{"id":"af128221-dac9-50bf-a03b-8f6ca41407f6","stable_key":"7edf94bb-95c8-5234-9161-9eb338bb9b36:boron-human-transport-negative-2013","predicate":"did_not_support","statement":"In the 2013 replication study, 10 mM borate did not change the SLC4A11-associated intracellular-pH response during a sodium-free pulse, arguing against sodium–borate cotransport.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"aad66e3c-b135-5851-b4a1-986bfa65d8e0","mechanism_event_label":"A direct follow-up failed to detect the borate transport predicted by the original model.","subject":{"id":"85fea21a-9b03-5b27-9588-e716d8390743","slug":"slc4a11","display_name":"Human SLC4A11 / NaBC1","entity_type_key":"protein"},"object":{"id":"edd42ff7-d4bf-546b-8403-52eabd4f0d5c","slug":"cellular-borate-transport","display_name":"Cellular borate transport","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"aad66e3c-b135-5851-b4a1-986bfa65d8e0","stable_key":"7edf94bb-95c8-5234-9161-9eb338bb9b36:boron-human-transport-negative-2013-event","event_type":"biochemical_relationship","label":"A direct follow-up failed to detect the borate transport predicted by the original model.","description":"In the 2013 replication study, 10 mM borate did not change the SLC4A11-associated intracellular-pH response during a sodium-free pulse, arguing against sodium–borate cotransport.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"04e68eab-58b9-5be0-95b1-0739fc0699ff","slug":"borate","display_name":"Tetrahydroxyborate / B(OH)4−","entity_type_key":"ion"},"role":"tested_substrate","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"85fea21a-9b03-5b27-9588-e716d8390743","slug":"slc4a11","display_name":"Human SLC4A11 / NaBC1","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"edd42ff7-d4bf-546b-8403-52eabd4f0d5c","slug":"cellular-borate-transport","display_name":"Cellular borate transport","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/boron-research/23864606.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"b35216315076720b687cb692519b340957bdadbeb1ce71ae26972aa301dd7df1\", \"start_char\": 0, \"end_char\": 1835, \"text_sha256\": \"b35216315076720b687cb692519b340957bdadbeb1ce71ae26972aa301dd7df1\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"HEK293 and NHE-deficient PS120 functional transport experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"10 mM borate during sodium removal/readdition; comparison with control cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Negative borate transport result applies to the tested assays. Sodium replacement and buffer chemistry were investigated; they do not establish a universal explanation of all discordant assays.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Boron research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"boron","display_name":"Boron","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Human SLC4A11 in heterologous cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A direct follow-up failed to detect the borate transport predicted by the original model.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[boron-p23864606] SLC4A11 is an EIPA-sensitive Na(+) permeable pHi regulator. (2013). https://pubmed.ncbi.nlm.nih.gov/23864606/ DOI: 10.1152/ajpcell.00056.2013","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Cell membrane; intracellular pH and sodium flux","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"3a95c1cc-4cbb-5cc4-b515-4fd7745d064f","evidence_kind":"source_excerpt","locator":"Lines 209-220","start_line":209,"end_line":220,"excerpt":"### boron-human-transport-negative-2013\nIn the 2013 replication study, 10 mM borate did not change the SLC4A11-associated intracellular-pH response during a sodium-free pulse, arguing against sodium–borate cotransport.\nCondition category: normal\nnutrient_topic: Boron research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A direct follow-up failed to detect the borate transport predicted by the original model.\norganism: Human SLC4A11 in heterologous cells\ntissue_or_cell_type: Cell membrane; intracellular pH and sodium flux\nexperimental_model: HEK293 and NHE-deficient PS120 functional transport experiments\nlimitations: Negative borate transport result applies to the tested assays. Sodium replacement and buffer chemistry were investigated; they do not establish a universal explanation of all discordant assays.\nexposure: 10 mM borate during sodium removal/readdition; comparison with control cells\nevidence_span: {\"source_cache\": \"artifacts/boron-research/23864606.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"b35216315076720b687cb692519b340957bdadbeb1ce71ae26972aa301dd7df1\", \"start_char\": 0, \"end_char\": 1835, \"text_sha256\": \"b35216315076720b687cb692519b340957bdadbeb1ce71ae26972aa301dd7df1\"}\n[boron-p23864606] SLC4A11 is an EIPA-sensitive Na(+) permeable pHi regulator. (2013). https://pubmed.ncbi.nlm.nih.gov/23864606/ DOI: 10.1152/ajpcell.00056.2013","model_system":"HEK293 and NHE-deficient PS120 functional transport experiments","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [boron-p23864606] SLC4A11 is an EIPA-sensitive Na(+) permeable pHi regulator. (2013). https://pubmed.ncbi.nlm.nih.gov/23864606/ DOI: 10.1152/ajpcell.00056.2013","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"2d96c547-aeec-5d8b-9d31-1288da209f89","stable_key":"import-7edf94bb-95c8-5234-9161-9eb338bb9b36","title":"Boron: chemistry, nutrient interactions, low-intake studies and mechanistic uncertainties (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"0a32c1c5c70cfb4a378f6ace35cf5b75d90ed3065ada91b9f9f64015d603c8e3","revision_id":"38f316f2-4344-542e-a638-0ac5402f678d","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[{"id":"8e9f266d-de06-58e2-bfe2-ed8125c1b430","title":"Does human SLC4A11 transport borate?","kind":"contradiction","status":"open","why":"The 2004 paper assigned sodium-coupled borate transport to human SLC4A11. Two later experimental studies failed to reproduce borate transport, including one with a functioning plant positive control. This is a disagreement in published functional assignments, not a correction to our source text. The 2013 full text discusses NMDG–borate buffer interactions as a possible source of apparent pH responses; assay and expression-system differences also require consideration.","resolution":"Retain all three findings and their exact study locations. Do not annotate human SLC4A11 as an established borate carrier. Later proton-conductance research and demonstrated transport by the pufferfish paralog remain separately scoped; neither silently replaces or resolves the historical human data.","created_at":"2026-09-17 19:08:59","record_type":"conflict","display_label":"Recorded conflict","record_url":"/conflicts/8e9f266d-de06-58e2-bfe2-ed8125c1b430","sides":[{"conflict_id":"8e9f266d-de06-58e2-bfe2-ed8125c1b430","ordinal":0,"label":"The original paper called SLC4A11 a borate transporter; later studies challenged this assignment.","revision_id":"38f316f2-4344-542e-a638-0ac5402f678d","start_line":196,"end_line":207,"quote":"### boron-human-transport-original\nThe 2004 NaBC1 study assigned human SLC4A11 electrogenic, sodium-coupled borate transport.\nCondition category: normal\nnutrient_topic: Boron research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The original paper called SLC4A11 a borate transporter; later studies challenged this assignment.\norganism: Human SLC4A11 expressed in experimental cells\ntissue_or_cell_type: Membrane transport assays\nexperimental_model: Heterologous mammalian transporter expression and functional assays\nlimitations: The borate-transport assignment is disputed by later direct experiments. This historical result remains visible as a genuine literature conflict, not accepted transporter annotation.\nexposure: Borate exposure with NaBC1 overexpression or knockdown\nevidence_span: {\"source_cache\": \"artifacts/boron-research/15525507.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"741b5972d5af120759f4100701b1f450c620182ffe6585a1b5049533961a6abe\", \"start_char\": 0, \"end_char\": 980, \"text_sha256\": \"741b5972d5af120759f4100701b1f450c620182ffe6585a1b5049533961a6abe\"}\n[boron-p15525507] NaBC1 is a ubiquitous electrogenic Na+ -coupled borate transporter essential for cellular boron homeostasis and cell growth and proliferation. (2004). https://pubmed.ncbi.nlm.nih.gov/15525507/ DOI: 10.1016/j.molcel.2004.09.030","source_key":"import-7edf94bb-95c8-5234-9161-9eb338bb9b36","source_title":"Boron: chemistry, nutrient interactions, low-intake studies and mechanistic uncertainties (2026-09-17)","claim_ids":["9672ab49-f919-58ac-aac0-dce1b6952b1e"]},{"conflict_id":"8e9f266d-de06-58e2-bfe2-ed8125c1b430","ordinal":1,"label":"A direct follow-up failed to detect the borate transport predicted by the original model.","revision_id":"38f316f2-4344-542e-a638-0ac5402f678d","start_line":209,"end_line":220,"quote":"### boron-human-transport-negative-2013\nIn the 2013 replication study, 10 mM borate did not change the SLC4A11-associated intracellular-pH response during a sodium-free pulse, arguing against sodium–borate cotransport.\nCondition category: normal\nnutrient_topic: Boron research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A direct follow-up failed to detect the borate transport predicted by the original model.\norganism: Human SLC4A11 in heterologous cells\ntissue_or_cell_type: Cell membrane; intracellular pH and sodium flux\nexperimental_model: HEK293 and NHE-deficient PS120 functional transport experiments\nlimitations: Negative borate transport result applies to the tested assays. Sodium replacement and buffer chemistry were investigated; they do not establish a universal explanation of all discordant assays.\nexposure: 10 mM borate during sodium removal/readdition; comparison with control cells\nevidence_span: {\"source_cache\": \"artifacts/boron-research/23864606.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"b35216315076720b687cb692519b340957bdadbeb1ce71ae26972aa301dd7df1\", \"start_char\": 0, \"end_char\": 1835, \"text_sha256\": \"b35216315076720b687cb692519b340957bdadbeb1ce71ae26972aa301dd7df1\"}\n[boron-p23864606] SLC4A11 is an EIPA-sensitive Na(+) permeable pHi regulator. (2013). https://pubmed.ncbi.nlm.nih.gov/23864606/ DOI: 10.1152/ajpcell.00056.2013","source_key":"import-7edf94bb-95c8-5234-9161-9eb338bb9b36","source_title":"Boron: chemistry, nutrient interactions, low-intake studies and mechanistic uncertainties (2026-09-17)","claim_ids":["af128221-dac9-50bf-a03b-8f6ca41407f6"]},{"conflict_id":"8e9f266d-de06-58e2-bfe2-ed8125c1b430","ordinal":2,"label":"A second study found no human SLC4A11 borate transport even though its positive control worked.","revision_id":"38f316f2-4344-542e-a638-0ac5402f678d","start_line":222,"end_line":233,"quote":"### boron-human-transport-negative-2016\nHuman SLC4A11 did not support borate-associated transport in Xenopus oocytes, whereas the plant NIP5;1 positive control did.\nCondition category: normal\nnutrient_topic: Boron research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A second study found no human SLC4A11 borate transport even though its positive control worked.\norganism: Human SLC4A11; Xenopus expression host\ntissue_or_cell_type: Membrane transport assays\nexperimental_model: Xenopus oocyte expression with plant positive control and HEK293 experiments\nlimitations: Species of protein and expression host are distinct. The human negative result does not exclude borate transport by other species or unrelated proteins.\nexposure: Borate-associated cell swelling; plant NIP5;1 positive control\nevidence_span: {\"source_cache\": \"artifacts/boron-research/27558157.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"a49d680cd492460159d231e0c55b053b2143ce17aaa902c97c087e5985e78ebd\", \"start_char\": 0, \"end_char\": 1823, \"text_sha256\": \"a49d680cd492460159d231e0c55b053b2143ce17aaa902c97c087e5985e78ebd\"}\n[boron-p27558157] Functional assessment of SLC4A11, an integral membrane protein mutated in corneal dystrophies. (2016). https://pubmed.ncbi.nlm.nih.gov/27558157/ DOI: 10.1152/ajpcell.00078.2016","source_key":"import-7edf94bb-95c8-5234-9161-9eb338bb9b36","source_title":"Boron: chemistry, nutrient interactions, low-intake studies and mechanistic uncertainties (2026-09-17)","claim_ids":["5a738ad5-aab1-56cb-8ca4-8e74a3633278"]}]}],"corrections":[],"research":null}