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chaperones","url":"https://pubmed.ncbi.nlm.nih.gov/23011926","citation_count":24,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"24010658","id":"PMC_24010658","title":"Sarcoplasmic reticulum K(+) (TRIC) channel does not carry essential countercurrent during Ca(2+) release.","date":"2013","source":"Biophysical journal","url":"https://pubmed.ncbi.nlm.nih.gov/24010658","citation_count":24,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"29095551","id":"PMC_29095551","title":"Genetic expansion of chaperonin-containing TCP-1 (CCT/TRiC) complex subunits yields testis-specific isoforms required for spermatogenesis in planarian flatworms.","date":"2017","source":"Molecular reproduction and development","url":"https://pubmed.ncbi.nlm.nih.gov/29095551","citation_count":24,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"27909292","id":"PMC_27909292","title":"Crystal structures of the TRIC trimeric intracellular cation channel orthologues.","date":"2016","source":"Cell research","url":"https://pubmed.ncbi.nlm.nih.gov/27909292","citation_count":23,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"24298020","id":"PMC_24298020","title":"Vaccinia-related kinase 2 mediates accumulation of polyglutamine aggregates via negative regulation of the chaperonin TRiC.","date":"2013","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/24298020","citation_count":22,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"4501841","id":"PMC_4501841","title":"Some consequences of the multiple infection of cell cultures by TRIC organisms.","date":"1972","source":"The Journal of hygiene","url":"https://pubmed.ncbi.nlm.nih.gov/4501841","citation_count":22,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"15538632","id":"PMC_15538632","title":"A new locus for nonsyndromic deafness DFNB49 maps to chromosome 5q12.3-q14.1.","date":"2004","source":"Human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/15538632","citation_count":21,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"31805819","id":"PMC_31805819","title":"TRIC-A Channel Maintains Store Calcium Handling by Interacting With Type 2 Ryanodine Receptor in Cardiac Muscle.","date":"2019","source":"Circulation research","url":"https://pubmed.ncbi.nlm.nih.gov/31805819","citation_count":21,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"30181275","id":"PMC_30181275","title":"The chaperonin TRiC/CCT is essential for the action of bacterial glycosylating protein toxins like Clostridium difficile toxins A and B.","date":"2018","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/30181275","citation_count":21,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"28963798","id":"PMC_28963798","title":"TRiC/CCT chaperonins are essential for maintaining myofibril organization, cardiac physiological rhythm, and lifespan.","date":"2017","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/28963798","citation_count":21,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"22097895","id":"PMC_22097895","title":"DFNB49 is an important cause of non-syndromic deafness in Czech Roma patients but not in the general Czech population.","date":"2011","source":"Clinical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/22097895","citation_count":21,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"37193829","id":"PMC_37193829","title":"Pathway and mechanism of tubulin folding mediated by TRiC/CCT along its ATPase cycle revealed using cryo-EM.","date":"2023","source":"Communications biology","url":"https://pubmed.ncbi.nlm.nih.gov/37193829","citation_count":20,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"27708139","id":"PMC_27708139","title":"Regulation of GPCR expression through an interaction with CCT7, a subunit of the CCT/TRiC complex.","date":"2016","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/27708139","citation_count":20,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"21856455","id":"PMC_21856455","title":"Chaperonins induce an amyloid-like transformation of ovine prion protein: the fundamental difference in action between eukaryotic TRiC and bacterial GroEL.","date":"2011","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/21856455","citation_count":20,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"26051097","id":"PMC_26051097","title":"Noninvasive detection of trophoblast protein signatures linked to early pregnancy loss using trophoblast retrieval and isolation from the cervix (TRIC).","date":"2015","source":"Fertility and sterility","url":"https://pubmed.ncbi.nlm.nih.gov/26051097","citation_count":19,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"16201870","id":"PMC_16201870","title":"Efficient production of native actin upon translation in a bacterial lysate supplemented with the eukaryotic chaperonin TRiC.","date":"2005","source":"Biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/16201870","citation_count":19,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"31432762","id":"PMC_31432762","title":"tRic: a user-friendly data portal to explore the expression landscape of tRNAs in human cancers.","date":"2019","source":"RNA biology","url":"https://pubmed.ncbi.nlm.nih.gov/31432762","citation_count":18,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"36715408","id":"PMC_36715408","title":"Recognition of the CCT5 di-Glu degron by CRL4DCAF12 is dependent on TRiC assembly.","date":"2023","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/36715408","citation_count":18,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"25666562","id":"PMC_25666562","title":"Molecular genetics of MARVELD2 and clinical phenotype in Pakistani and Slovak families segregating DFNB49 hearing loss.","date":"2015","source":"Human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/25666562","citation_count":18,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"4522724","id":"PMC_4522724","title":"Interactions of TRIC agents with macrophages: effects on lysosomal enzymes of the cell.","date":"1974","source":"The Journal of hygiene","url":"https://pubmed.ncbi.nlm.nih.gov/4522724","citation_count":18,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"39480921","id":"PMC_39480921","title":"Brain malformations and seizures by impaired chaperonin function of TRiC.","date":"2024","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/39480921","citation_count":17,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"29403048","id":"PMC_29403048","title":"Development of a yeast internal-subunit eGFP labeling strategy and its application in subunit identification in eukaryotic group II chaperonin TRiC/CCT.","date":"2018","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/29403048","citation_count":17,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"17417821","id":"PMC_17417821","title":"Conformational rearrangements of tail-less complex polypeptide 1 (TCP-1) ring complex (TRiC)-bound actin.","date":"2007","source":"Biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/17417821","citation_count":17,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"32330125","id":"PMC_32330125","title":"TRIC-A shapes oscillatory Ca2+ signals by interaction with STIM1/Orai1 complexes.","date":"2020","source":"PLoS biology","url":"https://pubmed.ncbi.nlm.nih.gov/32330125","citation_count":17,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"36921056","id":"PMC_36921056","title":"Structural basis of plp2-mediated cytoskeletal protein folding by TRiC/CCT.","date":"2023","source":"Science advances","url":"https://pubmed.ncbi.nlm.nih.gov/36921056","citation_count":16,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"37625406","id":"PMC_37625406","title":"A hierarchical assembly pathway directs the unique subunit arrangement of TRiC/CCT.","date":"2023","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/37625406","citation_count":16,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"25885414","id":"PMC_25885414","title":"MARVELD2 (DFNB49) mutations in the hearing impaired Central European Roma population--prevalence, clinical impact and the common origin.","date":"2015","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/25885414","citation_count":15,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"37348683","id":"PMC_37348683","title":"Absence of TRIC-B from type XIV Osteogenesis Imperfecta osteoblasts alters cell adhesion and mitochondrial function - A multi-omics study.","date":"2023","source":"Matrix biology : journal of the International Society for Matrix Biology","url":"https://pubmed.ncbi.nlm.nih.gov/37348683","citation_count":15,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"28387457","id":"PMC_28387457","title":"Dampened activity of ryanodine receptor channels in mutant skeletal muscle lacking TRIC-A.","date":"2017","source":"The Journal of physiology","url":"https://pubmed.ncbi.nlm.nih.gov/28387457","citation_count":15,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"18775504","id":"PMC_18775504","title":"The CCT/TRiC chaperonin is required for maturation of sphingosine kinase 1.","date":"2008","source":"The international journal of biochemistry & cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/18775504","citation_count":15,"is_preprint":false,"source_track":"pubmed_title"}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":43672,"output_tokens":416,"usd":0.068628},"stage2":{"model":"","input_tokens":0,"output_tokens":0,"usd":0.0},"total_usd":0.138942,"stage1_batch_id":"msgbatch_01Mgbec4vM6c9vXht7JVJzss","stage2_batch_id":"msgbatch_01JkuuH5RB2BdJNsgnhjbC6s","note":"batch pricing = 50% of standard","round2_stage1":{"model":"claude-sonnet-4-6","input_tokens":44101,"output_tokens":555,"usd":0.070314},"round2_rules_fired":"R1"},"stage1_raw":"Looking at the corpus, I need to identify papers about MARVELD2 (also known as tricellulin, associated with DFNB49 hearing loss). Let me scan through the abstracts carefully.\n\nThe vast majority of papers in this corpus are about TRiC/CCT chaperonin complex - these are symbol collisions (TRiC is an acronym for a completely different protein complex, not MARVELD2). MARVELD2 encodes tricellulin, a tricellular tight junction protein.\n\nPapers actually about MARVELD2/tricellulin:\n- PMID 18084694: Splice-site mutations in the TRIC gene (tricellulin/MARVELD2) causing ARNSHI hearing impairment\n- PMID 25666562: Molecular genetics of MARVELD2 and clinical phenotype (mentions mice homozygous for Marveld2 variant had defects in inner ear, heart, salivary gland, thyroid, olfactory epithelium)\n- PMID 22097895: DFNB49/MARVELD2 mutations in Roma patients\n- PMID 25885414: MARVELD2 mutations in Roma population\n- PMID 15538632: DFNB49 locus mapping (no mechanistic findings about MARVELD2 protein)\n\nNone of these abstracts describe direct mechanistic experiments about HOW the MARVELD2/tricellulin protein works (no Co-IP, enzymatic assay, structure, localization with functional consequence, etc.). They are genetic/clinical studies. No mechanistic discoveries can be extracted.\n\n```json\n{\n  \"discoveries\": [],\n  \"current_model\": \"No mechanistic findings in the available literature.\"\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\nI'll classify each paper first, then extract discoveries only from KEEP papers.\n\n**Classification:**\n\nMARVELD2 encodes tricellulin, a tricellular tight junction protein involved in hearing. The corpus is overwhelmingly about TRiC/CCT (chaperonin), TRIC channels (trimeric intracellular cation channels), TRIC agents (Chlamydia), or TRIC (trophoblast retrieval) — all unrelated to MARVELD2.\n\nPapers about MARVELD2/tricellulin/DFNB49:\n- Paper [46]: TRIC gene (tricellulin/MARVELD2) mutations in DFNB49 — KEEP (but genetic/linkage study, minimal mechanism)\n- Paper [81]: MARVELD2 gene mutations in Czech Roma DFNB49 — KEEP (but genetic/clinical, no mechanism)\n- Paper [89]: MARVELD2 mutations, DFNB49, clinical phenotype — KEEP (mentions tricellulin, tricellular tight junction protein, mouse phenotype)\n- Paper [97]: MARVELD2 mutations in Roma population — KEEP (genetic/prevalence, minimal mechanism)\n\nAll other papers are EXCLUDE (alias collisions: TRiC chaperonin complex, TRIC channels, TRIC agents/Chlamydia, TRIC trophoblast retrieval, tRic database).\n\n**Extraction from KEEP papers:**\n\nPapers [46], [81], [89], [97] are primarily genetic/epidemiological studies. Paper [89] mentions tricellulin as \"a tricellular tight junction protein\" and notes mouse models showing defects in inner ear, heart, mandibular salivary gland, thyroid gland and olfactory epithelium, but no direct mechanistic experiment is described beyond protein identity and loss-of-function phenotype in mice.\n\nNone of the KEPT papers contain direct mechanistic experiments (Co-IP, binding partner identification, enzymatic assay, structure, localization with functional consequence, etc.) about MARVELD2/tricellulin. They are genetic linkage/mutation studies.\n\n```json\n{\n  \"discoveries\": [],\n  \"current_model\": \"No mechanistic findings about MARVELD2 in the available literature (corpus appears contaminated with off-target papers).\"\n}\n```","stage2_raw":"\n\n--- ROUND 2 (refusal — no on-target evidence) ---\n"}