Science Advances最新文献

{"title":"Three modes of viral adaption by the heart","authors":"Cameron D. Griffiths,&nbsp;Millie Shah,&nbsp;William Shao,&nbsp;Cheryl A. Borgman,&nbsp;Kevin A. Janes","doi":"10.1126/sciadv.adp6303","DOIUrl":"10.1126/sciadv.adp6303","url":null,"abstract":"<div >Viruses elicit long-term adaptive responses in the tissues they infect. Understanding viral adaptions in humans is difficult in organs such as the heart, where primary infected material is not routinely collected. In search of asymptomatic infections with accompanying host adaptions, we mined for cardio-pathogenic viruses in the unaligned reads of nearly 1000 human hearts profiled by RNA sequencing. Among virus-positive cases (~20%), we identified three robust adaptions in the host transcriptome related to inflammatory nuclear factor κB (NF-κB) signaling and posttranscriptional regulation by the p38-MK2 pathway. The adaptions are not determined by the infecting virus, and they recur in infections of human or animal hearts and cultured cardiomyocytes. Adaptions switch states when NF-κB or p38-MK2 is perturbed in cells engineered for chronic infection by the cardio-pathogenic virus, coxsackievirus B3. Stratifying viral responses into reversible adaptions adds a targetable systems-level simplification for infections of the heart and perhaps other organs.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adp6303","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxic small alarmone synthetase FaRel2 inhibits translation by pyrophosphorylating tRNAGly and tRNAThr","authors":"Tatsuaki Kurata,&nbsp;Masaki Takegawa,&nbsp;Takayuki Ohira,&nbsp;Egor A. Syroegin,&nbsp;Gemma C. Atkinson,&nbsp;Marcus J.O. Johansson,&nbsp;Yury S. Polikanov,&nbsp;Abel Garcia-Pino,&nbsp;Tsutomu Suzuki,&nbsp;Vasili Hauryliuk","doi":"10.1126/sciadv.adr9624","DOIUrl":"10.1126/sciadv.adr9624","url":null,"abstract":"<div >Translation-targeting toxic small alarmone synthetases (toxSAS) are effectors of bacterial toxin-antitoxin systems that pyrophosphorylate the 3′-CCA end of transfer RNA (tRNA) to prevent aminoacylation. toxSAS are implicated in antiphage immunity: Phage detection triggers the toxSAS activity to shut down viral production. We show that the toxSAS FaRel2 inspects the tRNA acceptor stem to specifically select tRNA^Gly and tRNA^Thr. The first, second, fourth, and fifth base pairs of the stem act as the specificity determinants. We show that the toxSASs PhRel2 and CapRel^SJ46 differ in tRNA specificity from FaRel2 and rationalize this through structural modeling: While the universal 3′-CCA end slots into a highly conserved CCA recognition groove, the acceptor stem recognition region is variable across toxSAS diversity. As phages use tRNA isoacceptors to overcome tRNA-targeting defenses, we hypothesize that highly evolvable modular tRNA recognition allows for the escape of viral countermeasures through tRNA substrate specificity switching.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adr9624","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"USP1 deubiquitinates PARP1 to regulate its trapping and PARylation activity","authors":"Anna Nespolo,&nbsp;Linda Stefenatti,&nbsp;Ilenia Pellarin,&nbsp;Alice Gambelli,&nbsp;Gian Luca Rampioni Vinciguerra,&nbsp;Javad Karimbayli,&nbsp;Sara Barozzi,&nbsp;Fabrizio Orsenigo,&nbsp;Riccardo Spizzo,&nbsp;Milena S. Nicoloso,&nbsp;Ilenia Segatto,&nbsp;Sara D’Andrea,&nbsp;Michele Bartoletti,&nbsp;Emilio Lucia,&nbsp;Giorgio Giorda,&nbsp;Vincenzo Canzonieri,&nbsp;Fabio Puglisi,&nbsp;Barbara Belletti,&nbsp;Monica Schiappacassi,&nbsp;Gustavo Baldassarre,&nbsp;Maura Sonego","doi":"10.1126/sciadv.adp6567","DOIUrl":"10.1126/sciadv.adp6567","url":null,"abstract":"<div >PARP inhibitors (PARPi) represent a game-changing treatment for patients with ovarian cancer with tumors deficient for the homologous recombination (HR) pathway treated with platinum (Pt)–based therapy. PARPi exert their cytotoxic effect by both trapping PARP1 on the damaged DNA and by restraining its enzymatic activity (PARylation). How PARP1 is recruited and trapped at the DNA damage sites and how resistance to PARPi could be overcome are still matters of investigation. Here, we described PARP1 as a substrate of the deubiquitinase USP1. At molecular level, USP1 binds PARP1 to remove its K63-linked polyubiquitination and controls PARP1 chromatin trapping and PARylation activity, regulating sensitivity to PARPi. In both Pt/PARPi-sensitive and -resistant cells, USP1/PARP1 combined blockade enhances replicative stress, DNA damage, and cell death. Our work dissected the biological interaction between USP1 and PARP1 and recommended this axis as a promising and powerful therapeutic choice for not only sensitive but also chemoresistant patients with ovarian cancer irrespective of their HR status.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adp6567","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Forecast skill assessment of an operational continental heat-cold-health forecasting system: New avenues for health early warning systems","authors":"Marcos Quijal-Zamorano,&nbsp;Desislava Petrova,&nbsp;Èrica Martínez-Solanas,&nbsp;François R. Herrmann,&nbsp;Xavier Rodó,&nbsp;Jean-Marie Robine,&nbsp;Marc Marí-Dell’Olmo,&nbsp;Hicham Achebak,&nbsp;Joan Ballester","doi":"10.1126/sciadv.ado5286","DOIUrl":"10.1126/sciadv.ado5286","url":null,"abstract":"<div >More than 110,000 Europeans died as a result of the record-breaking temperatures of 2022 and 2023. A new generation of impact-based early warning systems, using epidemiological models to transform weather forecasts into health forecasts for targeted population subgroups, is an essential adaptation strategy to increase resilience against climate change. Here, we assessed the skill of an operational continental heat-cold-health forecasting system. We used state-of-the-art temperature-lag-mortality epidemiological models to transform bias-corrected ensemble weather forecasts into daily temperature-related mortality forecasts. We found that temperature forecasts can be used to issue skillful forecasts of temperature-related mortality. However, the forecast skill varied by season and location, and it was different for temperature and temperature-related mortality due to the use of epidemiological models. Overall, our study demonstrates and quantifies the forecast skill horizon of heat-cold-health forecasting systems, which is a necessary step toward generating trust among public health authorities and end users.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ado5286","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TET2 regulates early and late transitions in exhausted CD8+ T cell differentiation and limits CAR T cell function","authors":"Alexander J. Dimitri,&nbsp;Amy E. Baxter,&nbsp;Gregory M. Chen,&nbsp;Caitlin R. Hopkins,&nbsp;Geoffrey T. Rouin,&nbsp;Hua Huang,&nbsp;Weimin Kong,&nbsp;Christopher H. Holliday,&nbsp;Volker Wiebking,&nbsp;Robert Bartoszek,&nbsp;Sydney Drury,&nbsp;Katherine Dalton,&nbsp;Owen M. Koucky,&nbsp;Zeyu Chen,&nbsp;Josephine R. Giles,&nbsp;Alexander T. Dils,&nbsp;In-Young Jung,&nbsp;Roddy O’Connor,&nbsp;Sierra Collins,&nbsp;John K. Everett,&nbsp;Kevin Amses,&nbsp;Scott Sherrill-Mix,&nbsp;Aditi Chandra,&nbsp;Naomi Goldman,&nbsp;Golnaz Vahedi,&nbsp;Julie K. Jadlowsky,&nbsp;Regina M. Young,&nbsp;Jan Joseph Melenhorst,&nbsp;Shannon L. Maude,&nbsp;Bruce L. Levine,&nbsp;Noelle V. Frey,&nbsp;Shelley L. Berger,&nbsp;Stephan A. Grupp,&nbsp;David L. Porter,&nbsp;Friederike Herbst,&nbsp;Matthew H. Porteus,&nbsp;Shannon A. Carty,&nbsp;Frederic D. Bushman,&nbsp;Evan W. Weber,&nbsp;E. John Wherry,&nbsp;Martha S. Jordan,&nbsp;Joseph A. Fraietta","doi":"10.1126/sciadv.adp9371","DOIUrl":"10.1126/sciadv.adp9371","url":null,"abstract":"<div >CD8⁺ T cell exhaustion hampers control of cancer and chronic infections and limits chimeric antigen receptor (CAR) T cell efficacy. Targeting <i>TET2</i> in CAR T cells provides therapeutic benefit; however, TET2’s role in exhausted T cell (T_EX) development is unclear. In chronic lymphocytic choriomeningitis virus (LCMV) infection, TET2 drove conversion from stem cell–like T_EX progenitors toward terminally differentiated and effector (T_EFF)–like T_EX. TET2 also enforced a terminally differentiated state in the early bifurcation between T_EFF and T_EX, indicating broad roles for TET2 in acquisition of effector biology. To exploit the therapeutic potential of TET2, we developed clinically actionable <i>TET2-</i>targeted CAR T cells by disrupting <i>TET2</i> via knock-in of a safety switch alongside CAR knock-in at the <i>TRAC</i> locus. <i>TET2</i>-targeted CAR T cells exhibited restrained terminal exhaustion in vitro and enhanced antitumor responses in vivo. Thus, TET2 regulates fate transitions in T_EX differentiation and can be targeted with a safety mechanism in CAR T cells for improved tumor control.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adp9371","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Achieving strong optical nonlinearity and wide bandgap of pnictides via ionic motif–driven directed assembly of covalent groups","authors":"Lihua Gao,&nbsp;Jindong Chen,&nbsp;Xuemei Shi,&nbsp;Yan Xiao,&nbsp;Yinglei Han,&nbsp;Chensheng Lin,&nbsp;Huikang Jiang,&nbsp;Guangsai Yang,&nbsp;Guang Peng,&nbsp;Ning Ye","doi":"10.1126/sciadv.adr2389","DOIUrl":"10.1126/sciadv.adr2389","url":null,"abstract":"<div >Noncentrosymmetric (NCS) pnictides are indispensable for nonlinear optics, ferroelectrics, magnetic Weyl electronics, etc., areas, yet their structure design remains a substantial challenge. By using asymmetric ionic unit–driven covalent groups orienting and rigidity-flexibility coupling dual strategy, we successfully design and synthesize four NCS pnictides: [Sr₄Br]₂[M^II₃Si₂₅P₄₀] (M^II = Mg, Cd) and [Ba₃Br][M^IIISi₁₀P₁₆] (M^III = Ga, In), which exhibit strong second harmonic generation effects (5.2 to 7.5 × AgGaS₂), wide bandgaps (1.81 to 1.90 electron volts), and moderate birefringence (0.030 to 0.051). An unprecedented NCS structure-inducing mechanism analysis revealed that the (Sr₄Br) and (Ba₄Br) ionic units featuring the diamond-like electrostatic force field effectively break inversion symmetry and trigger uniform arrangement of the covalent tetrahedron groups. Furthermore, the nonlinear optical (NLO) properties and birefringence can be remarkably tuned by the secondary covalent building blocks (M^II/IIIP₄ tetrahedra) with distinct bond flexibility providing a broader space for regulating the key parameters. This work might expand chemical space for exploiting high-performance pnictide NLO materials.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adr2389","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Compact highly sensitive photothermal RT-LAMP chip for simultaneous multidisease detection","authors":"Wenshang Guo,&nbsp;Ye Tao,&nbsp;Ruizhe Yang,&nbsp;Kaihao Mao,&nbsp;Hongwei Zhou,&nbsp;Minghui Xu,&nbsp;Tie Sun,&nbsp;Xiao Li,&nbsp;Changrui Shi,&nbsp;Zhenyou Ge,&nbsp;Rui Xue,&nbsp;Haizhou Zhou,&nbsp;Yukun Ren","doi":"10.1126/sciadv.adq2899","DOIUrl":"10.1126/sciadv.adq2899","url":null,"abstract":"<div >Developing instant detection systems with disease diagnostic capabilities holds immense importance for remote or resource-limited areas. However, the task of creating these systems—which are simultaneously easy to operate, rapid in detection, and cost-effective—remains a challenge. In this study, we present a compact highly sensitive photothermal reverse transcriptase–loop-mediated isothermal amplification (RT-LAMP) chip (SPRC) designed for the detection of multiple diseases. The nucleic acid (NA) amplification on the chip is achieved through LAMP driven by either LED illumination or simple sunlight focusing. SPRC performs sample addition and amplification within a limited volume and autonomous enrichment of NA during the sample addition process, achieving a limit of detection (LOD) as low as 0.2 copies per microliter. Through 120 clinical samples, we achieved an accuracy of 95%, with a specificity exceeding 97.5%. Overall, SPRC has achieved promising progress in the application of point-of-care testing (POCT) by using light energy to simultaneously detect multiple diseases.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adq2899","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breaking Abbe’s diffraction limit with harmonic deactivation microscopy","authors":"Kevin Murzyn,&nbsp;Maarten L. S. van der Geest,&nbsp;Leo Guery,&nbsp;Zhonghui Nie,&nbsp;Pieter van Essen,&nbsp;Stefan Witte,&nbsp;Peter M. Kraus","doi":"10.1126/sciadv.adp3056","DOIUrl":"10.1126/sciadv.adp3056","url":null,"abstract":"<div >Nonlinear optical microscopy provides elegant means for label-free imaging of biological samples and condensed matter systems. The widespread areas of application could even be increased if resolution was improved, which the famous Abbe diffraction limit now restrains. Super-resolution techniques can break the diffraction limit but most rely on fluorescent labeling. This makes them incompatible with (sub)femtosecond temporal resolution and applications that demand the absence of labeling. Here, we introduce harmonic deactivation microscopy (HADES) for breaking the diffraction limit in nonfluorescent samples. By controlling the harmonic generation process on the quantum level with a second donut-shaped pulse, we confine the third-harmonic generation to three times below the original focus size of a scanning microscope. We demonstrate that resolution improvement by deactivation is more efficient for higher harmonic orders and only limited by the maximum applicable deactivation-pulse fluence. This provides a route toward sub-100-nanometer resolution in a regular nonlinear microscope.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adp3056","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ekman revisited: Surface currents to the left of the winds in the Northern Hemisphere","authors":"Michael J. McPhaden,&nbsp;K. Athulya,&nbsp;M. S. Girishkumar,&nbsp;Mirko Orlić","doi":"10.1126/sciadv.adr0282","DOIUrl":"10.1126/sciadv.adr0282","url":null,"abstract":"<div >Ekman’s theory of wind-driven ocean currents on a rotating planet is central to our understanding of why surface currents are deflected to the right of the winds in the Northern Hemisphere and to the left of the winds in the Southern Hemisphere. The theory admits solutions for currents deflected in the opposite direction at periods shorter than the local inertial period, but Ekman did not mention these currents, and they have only rarely been observed. Here, we describe a prominent example of surface flow in the Bay of Bengal directed to the left of clockwise-rotating land breeze wind forcing using multiple years of data from a long-term deepwater surface moored buoy. We further refine Ekman’s theory so as to better reconcile it with our own and previous measurements and then conclude by discussing the broad implications of this work for understanding wind-forced ocean circulation.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adr0282","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The vacuolar K+/H+ exchangers and calmodulin-like CML18 constitute a pH-sensing module that regulates K+ status in Arabidopsis","authors":"Miguel Daniel-Mozo,&nbsp;Belén Rombolá-Caldentey,&nbsp;Imelda Mendoza,&nbsp;Paula Ragel,&nbsp;Anna De Luca,&nbsp;Raul Carranco,&nbsp;Ana M. Alcaide,&nbsp;Alessio Ausili,&nbsp;Beatriz Cubero,&nbsp;Karin Schumacher,&nbsp;Francisco J. Quintero,&nbsp;Armando Albert,&nbsp;José M. Pardo","doi":"10.1126/sciadv.adp7658","DOIUrl":"10.1126/sciadv.adp7658","url":null,"abstract":"<div >Shifts in cytosolic pH have been recognized as key signaling events and mounting evidence supports the interdependence between H⁺ and Ca²⁺ signaling in eukaryotic cells. Among the cellular pH-stats, K⁺/H⁺ exchange at various membranes is paramount in plant cells. Vacuolar K⁺/H⁺ exchangers of the NHX (Na⁺,K⁺/H⁺ exchanger) family control luminal pH and, together with K⁺ and H⁺ transporters at the plasma membrane, have been suggested to also regulate cytoplasmic pH. We show the regulation of vacuolar K⁺/H⁺ exchange by cytoplasmic pH and the calmodulin-like protein CML18 in Arabidopsis. The crystal structure and physicochemical properties of CML18 indicate that this protein senses pH shifts. Interaction of CML18 with tonoplast exchangers NHX1 and NHX2 was favored at acidic pH, a physiological condition elicited by K⁺ starvation in Arabidopsis roots, whereas excess K⁺ produced cytoplasmic alkalinization and CML18 dissociation. These results imply that the pH-responsive NHX-CML18 module is an essential component of the cellular K⁺- and pH-stats.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adp7658","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}