Base by Base

Owino BO et al., PNAS - Using TurboID proximity proteomics and microscopy, researchers identify KIAP4 as the canonical member of a conserved Adhesion Related NTPase-like Domain (ARND) family that localizes to the Leishmania adhesion plaque. Deleting KIAP4 disrupts haptomonad adhesion in vitro and prevents colonization of the sand fly stomodeal valve without blocking metacyclogenesis. Key terms: Leishmania, adhesion, KIAP4, ARND family, sand fly.

Study Highlights:
TurboID::KIAP3 proximity labeling and mass spectrometry identified KIAP4 and multiple ARND family paralogs enriched at the adhered flagellum. KIAP4 colocalizes with KIAP3 at the adhesion plaque and accumulates during haptomonad differentiation. KIAP4 deletion severely reduces in vitro adhesion and abolishes stomodeal valve colonization in Lutzomyia longipalpis, while ARND paralogs are conserved across kinetoplastids and localize to adhered flagella in Trypanosoma congolense.

Conclusion:
KIAP4 is a foundational adhesion-plaque protein of a conserved ARND family required for Leishmania haptomonad adhesion and stomodeal valve colonization, making the family a potential target for transmission-blocking strategies.

Music:
Enjoy the music based on this article at the end of the episode.

Article title:
Identifcation of a conserved gene family with an essential role in Leishmania parasite–insect vector adhesion

First author:
Owino BO

Journal:
PNAS

DOI:
10.1073/pnas.2603653123

Reference:
Owino BO, Sunter JD, et al. Identifcation of a conserved gene family with an essential role in Leishmania parasite–insect vector adhesion. Proc Natl Acad Sci U S A (PNAS). 2026;123(30):e2603653123. doi:10.1073/pnas.2603653123

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

Support:
Base by Base is independent and ad-free — no sponsors, no paywall. If an episode was worth your time, chip in and keep the papers audited and the original songs coming:
❤️ Support monthly: https://buy.stripe.com/cNifZhclVebvagk2JDgEg01
☕ One-time donation: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00
More at basebybase.com

On PaperCast Base by Base you'll discover the latest in genomics, functional genomics, structural genomics, and proteomics.

Episode link: https://basebybase.com/episodes/kiap4-arnd-leishmania-adhesion

QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-08-08.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited sections cover: identification of KIAP4 as canonical ARND member; TurboID proximity-labeling workflow and enrichment results; KIAP4 localization to the adhesion plaque; KIAP4 deletion effects on in vitro adhesion and sand fly stomodeal valve colonization; ARND conservation across kinetoplastids; ARND domain arc
- transcript topics: KIAP4 as canonical ARND member localizes to adhesion plaque; TurboID proximity labeling workflow and enriched protein cohort; Localization of ARND paralogs in Leishmania and Trypanosoma congolense; KIAP4 deletion phenotype: impaired adhesion and valve colonization; KIAP4 add-back rescues adhesion defects; ARND domain architecture and Walker A motif absence (inactive NTPase-like domains)

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 4
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article_title
- article_journal
- license

Factual Items Audited:
- KIAP4 is the canonical member of the ARND family and localizes to the adhesion plaque
- ARND family is conserved across kinetoplastids; T. congolense paralogs localize to the adhered flagellum
- Deletion of KIAP4 severely impairs haptomonad adhesion and prevents stomodeal valve colonization in sand flies
- Walker A motif is not conserved in ARND p-loop NTPase domains, suggesting inactive enzymatic activity and a scaffolding role
- TurboID identified 58 candidate proteins enriched at the adhered flagellum; 32 localized to the adhered flagellum
- KIAP4 knockout does not block metacyclogenesis; metacyclic forms are present in KIAP4 mutants

QC result: Pass.

Ember M et al., PNAS - This episode examines a cryo-EM study of Escherichia coli tRNA-guanine transglycosylase (TGT) that solves the enzyme structure and its covalent intermediate with tRNATyr. Unexpectedly, the TGT homodimer can form covalent intermediates with two tRNAs simultaneously. The work maps peripheral RNA-binding residues required for activity and uses those insights to design higher-affinity dual-TAG RNA substrates for improved RNA-TAG labeling. Key terms: tRNA-guanine transglycosylase, cryo-EM, tRNA modification, RNA-TAG, Escherichia coli.

Study Highlights:
Using cryo-EM, the authors solved E. coli TGT and its covalent intermediate with tRNATyr and observed that the functional homodimer can form covalent intermediates with two tRNAs, displaying C2 symmetry. They identify peripheral residues (K285, K292, R320, Y35) and a dynamic loop (L98–I104) that stabilize the flipped anticodon loop and are required for covalent intermediate formation. Mutational analysis shows loss of activity for key substitutions, and structure-guided design of dual TAG32 hairpins yields markedly higher-affinity RNA substrates for RNA-TAG labeling. Biophysical assays estimate TAG3 KD ~3–5 µM versus dual TAG32 KD ~0.7–1 µM.

Conclusion:
The cryo-EM structures revise the canonical model of TGT function by demonstrating dual-substrate engagement and revealing peripheral binding determinants that enable both antibiotic-targeting strategies and improved, high-affinity RNA-labeling reagents.

Music:
Enjoy the music based on this article at the end of the episode.

Article title:
Cryo-EM reveals that Escherichia coli tRNA-transglycosylase can bind and act upon two tRNAs

First author:
Ember M

Journal:
PNAS

DOI:
10.1073/pnas.2601895123

Reference:
Ember M. Rutha, Mariusz Matyszewski, Alexander Harjung, Jaehee Park, Caroline Knittel, Evan McCormack, and Neal K. Devaraja. Cryo-EM reveals that Escherichia coli tRNA-transglycosylase can bind and act upon two tRNAs. PNAS. 2026;123:e2601895123. doi:10.1073/pnas.2601895123

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

Support:
Base by Base is independent and ad-free — no sponsors, no paywall. If an episode was worth your time, chip in and keep the papers audited and the original songs coming:
❤️ Support monthly: https://buy.stripe.com/cNifZhclVebvagk2JDgEg01
☕ One-time donation: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00
More at basebybase.com

On PaperCast Base by Base you'll discover the latest in genomics, functional genomics, structural genomics, and proteomics.

Episode link: https://basebybase.com/episodes/ecoli-tgt-dual-trna-cryoem

QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-08-07.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited sections describing (i) the cryo-EM structure of E. coli TGT and its covalent intermediates with tRNA, (ii) binding of two tRNAs and C2 symmetry, (iii) peripheral RNA-binding residues and their mutational analyses, (iv) the L98–I104 dynamic loop and A37 flipping, (v) Y35 involvement, (vi) R112 cross-monomer int
- transcript topics: Cryo-EM structure of E. coli TGT and covalent intermediate; Dual tRNA binding and C2 symmetry; Peripheral RNA-binding residues outside active site (K285, K292, R320, Y35, R112); Dynamic loop L98–I104 and anticodon loop A37 flipping; Mutational analyses and effects on covalent intermediate formation; Structure-based design of dual TAG32 hairpins and KD measurements

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 7
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article_title
- article_journal
- license

Factual Items Audited:
- E. coli TGT dimer can bind two tRNAs simultaneously and form covalent intermediates at both active sites
- Catalytic residue D264 participates in covalent intermediate formation at the active site
- External RNA-binding residues K285, K292, and R320 stabilize tRNA binding outside the active site; mutations (K285D, K292D, R320D) impair activity
- Y35 interacts with the RNA backbone and its mutation (Y35F) reduces covalent intermediate formation
- R112 cross-monomer interaction stabilizes tRNA across monomers but plays a secondary role in function
- A 180° flip of the tRNA anticodon loop (A37) is stabilized by the L98–I104 loop becoming ordered upon binding

QC result: Pass.

Ishiya K et al., PNAS - This episode examines a PNAS study that reports two high-coverage ancient human genomes from mainland Japan (an Initial Jomon >67× and a Middle Yayoi >46×). The genomes enable diploid genotyping, demographic reconstructions, ancestry modeling, and AMY1 copy-number analysis that reshape understanding of Jomon and Yayoi histories. Key terms: ancient DNA, Jomon, Yayoi, AMY1, population history.

Study Highlights:
The authors sequenced two low-contamination, high-coverage genomes from mainland Japan (IY1, Initial Jomon; DO, Middle Yayoi) enabling diploid analyses and CNV inference. Demographic reconstructions show divergent post-LGM trajectories: long-term stability with no expansion in the Jomon lineage and gradual sustained growth in the Yayoi-related ancestral population. Admixture and f-statistics indicate substantial continental Northeast Asian ancestry in the Yayoi individual and genetic continuity between the Yayoi and present-day mainland Japanese. High AMY1 copy numbers (~9–10) in both individuals suggest starch-relevant variation existed before large-scale rice farming.

Conclusion:
High-coverage ancient genomes from mainland Japan reveal contrasting population histories for Jomon and Yayoi lineages and show that elevated AMY1 copy-number variation relevant to starch consumption predates intensive rice agriculture, refining models of Japanese population formation.

Music:
Enjoy the music based on this article at the end of the episode.

Article title:
High-coverage ancient genomes reveal divergent population histories and prehistoric starch-related genetic variation in Japan

First author:
Ishiya K

Journal:
PNAS

DOI:
10.1073/pnas.2606162123

Reference:
Ishiya K., Mizuno F., Gojobori J., Kumagai M., et al. High-coverage ancient genomes reveal divergent population histories and prehistoric starch-related genetic variation in Japan. Proc Natl Acad Sci U S A. 2026;123(30):e2606162123. doi:10.1073/pnas.2606162123

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

Support:
Base by Base is independent and ad-free — no sponsors, no paywall. If an episode was worth your time, chip in and keep the papers audited and the original songs coming:
❤️ Support monthly: https://buy.stripe.com/cNifZhclVebvagk2JDgEg01
☕ One-time donation: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00
More at basebybase.com

On PaperCast Base by Base you'll discover the latest in genomics, functional genomics, structural genomics, and proteomics.

Episode link: https://basebybase.com/episodes/high-coverage-ancient-genomes-japan

QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-08-06.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited the transcript sections describing (1) sampling of two high-coverage genomes (IY1 and DO), (2) authenticity checks and sequencing depth, (3) demographic inferences (PSMC/SMC++), (4) AMY1 copy-number findings, (5) ancestry and admixture contexts, (6) admixture timing, and (7) the dual-structure model; excluded n
- transcript topics: Two high-coverage mainland Japan genomes (IY1 Jomon, DO Yayoi); Petrous bone sampling and ancient DNA authentication; PSMC/SMC++ demographic inferences post-LGM; AMY1 copy-number variation and starch-diet adaptation; Ancestry and continental admixture in Yayoi vs Jomon; Admixture timing via LD decay and related methods

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 5
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article_title
- article_journal
- license

Factual Items Audited:
- Two high-coverage ancient genomes from mainland Japan were analyzed: IY1 (Initial Jomon) and DO (Middle Yayoi).
- IY1: ~67-fold autosome coverage; DO: ~46-fold autosome coverage.
- AMY1 copy-number is high in both individuals: IY1 ~9 copies; DO ~10 copies.
- Yayoi individual DO shows continental Northeast Asian ancestry; Jomon individual IY1 shows basal East Asian ancestry.
- Admixture between Jomon and Yayoi occurred roughly 65–79 generations ago.
- Present-day Japanese are modeled as a dual-structure mixture of Jomon and Yayoi lineages.

QC result: Pass.

Wu G et al., Proceedings of the National Academy of Sciences - This episode examines a PNAS study that identifies site-specific lactylation of HSP90α as a metabolic signal linking glycolysis to mitochondrial biogenesis in ovarian cells. Lactylation at K58 and K616 modulates HSP90α phosphorylation, enabling nuclear import of PGC1α and LRPGC1, boosting mitochondrial number, cholesterol import, estradiol synthesis, and follicle growth; CREBBP, ACSS2 and GTPSCS participate in the lactylation pathway. Key terms: HSP90α, lactylation, PGC1α, mitochondrial biogenesis, estradiol.

Study Highlights:
The authors show that sodium lactate promotes HSP90α lactylation at K58 and K616 via CREBBP and lactyl-CoA synthesis (ACSS2/GTPSCS). K58 lactylation enhances ULK1 recruitment and S39 phosphorylation while K616 lactylation blocks CDK5-mediated S596 phosphorylation, together enabling HSP90α to chaperone PGC1α and LRPGC1 into the nucleus. Nuclear PGC1α/LRPGC1 activate NRF1/2 targets (Tfb1m, Tfb2m, Tfam) to drive mitochondrial biogenesis, increase mitochondrial cholesterol import and raise estradiol production, with in vivo lactate raising ovarian mtDNA, TOM20, estradiol and antral follicle number.

Conclusion:
Site-specific lactylation of HSP90α integrates glycolytic flux with chaperone and phosphorylation control to promote PGC1α/LRPGC1 nuclear import, mitochondrial biogenesis and steroidogenic output in ovarian cells, revealing a metabolite-dependent regulatory axis with potential implications for ovarian function and fertility.

Music:
Enjoy the music based on this article at the end of the episode.

Article title:
HSP90α lactylation orchestrates PGC1α and LRPGC1 nuclear translocation driving mitochondrial biogenesis

First author:
Wu G

Journal:
Proceedings of the National Academy of Sciences

DOI:
10.1073/pnas.2528979123

Reference:
Wu G., Li H., He T., et al. HSP90α lactylation orchestrates PGC1α and LRPGC1 nuclear translocation driving mitochondrial biogenesis. PNAS. 2026;123(30):e2528979123. doi:10.1073/pnas.2528979123

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

Support:
Base by Base is independent and ad-free — no sponsors, no paywall. If an episode was worth your time, chip in and keep the papers audited and the original songs coming:
❤️ Support monthly: https://buy.stripe.com/cNifZhclVebvagk2JDgEg01
☕ One-time donation: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00
More at basebybase.com

On PaperCast Base by Base you'll discover the latest in genomics, functional genomics, structural genomics, and proteomics.

Episode link: https://basebybase.com/episodes/hsp90a-lactylation-mito-biogenesis

QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-07-23.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited the main mechanistic narrative from lactate signaling to HSP90α lactylation, ULK1/CDK5-regulated phosphorylation, nuclear import of PGC1α/LRPGC1, NRF1/2-driven transcription, mitochondrial biogenesis, cholesterol import, and in vivo hormonal/follicle outcomes.
- transcript topics: Lactate as signaling molecule and lactylation concept; HSP90α lactylation at K58 and K616; CREBBP as the lactyltransferase and lactyl-CoA synthesis pathway; ULK1 and CDK5 regulation of S39 and S596 phosphorylation; HSP90α-mediated nuclear import of PGC1α and LRPGC1; NRF1/NRF2 target gene activation (TFB1M, TFB2M, Tfam) and mitochondrial biogenesis

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 5
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article_title
- article_journal
- license

Factual Items Audited:
- Lactate promotes nuclear translocation of PGC1α and LRPGC1 in granulosa/cell models.
- HSP90α lactylation occurs at K58 and K616; these sites regulate ULK1 recruitment and CDK5 docking, modulating S39 and S596 phosphorylation.
- CREBBP is the lactyltransferase for HSP90α; lactylation depends on Lactyl-CoA produced by ACSS2/GTPSCS.
- Lactylated HSP90α enhances binding to PGC1α/LRPGC1 and enables NRF1/2-driven transcription of mitochondrial biogenesis genes (TFB1M, Tfb2M, Tfam).
- Lactate increases mitochondrial biogenesis markers (mtDNA, TOM20) and cholesterol import into mitochondria, boosting estrogen production in vitro; in vivo lactate elevates estradio

QC result: Pass.

Mukhamedova L et al., Proceedings of the National Academy of Sciences - Using cryo-electron tomography and single-particle cryo-EM of infected Cos-7 cells, the authors show that echovirus 18 (E18) releases its RNA in vivo by capsid opening with loss of one to three pentamers. Binding to the neonatal Fc receptor (FcRn) expels VP1 pocket factors and primes particles for uncoating. Activated intermediates were not detected in cells, indicating rapid genome release. Key terms: echovirus 18, enterovirus, genome release, capsid opening, FcRn.

Study Highlights:
Cryo-EM/ET of infected cells resolved genome-containing E18 particles to 4.3 Å and imaged empty and open capsids in situ. Binding of E18 to FcRn induces partial expulsion of VP1 pocket factors, consistent with receptor- triggered priming. Empty capsids observed inside cells lack one to three pentamers of capsid proteins, providing direct evidence of capsid opening as the genome release mechanism. Activated particles were not detected in cells, implying these intermediates are short- lived and genome release is rapid.

Conclusion:
Capsid opening is the physiological uncoating mechanism of echovirus 18 in infected cells: receptor (FcRn) binding expels pocket factors and primes particles, and genome release occurs rapidly via loss of one to several pentamers with empty, incomplete capsids observed in situ.

Music:
Enjoy the music based on this article at the end of the episode.

Article title:
Particles of echovirus 18 open to release their genomes in vivo

First author:
Mukhamedova L

Journal:
Proceedings of the National Academy of Sciences

DOI:
10.1073/pnas.2601182123

Reference:
Mukhamedova L., Buchta D., Hrebík D., et al. Particles of echovirus 18 open to release their genomes in vivo. PNAS. 2026;123(30):e2601182123. https://doi.org/10.1073/pnas.2601182123

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

Support:
Base by Base is independent and ad-free — no sponsors, no paywall. If an episode was worth your time, chip in and keep the papers audited and the original songs coming:
❤️ Support monthly: https://buy.stripe.com/cNifZhclVebvagk2JDgEg01
☕ One-time donation: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00
More at basebybase.com

On PaperCast Base by Base you'll discover the latest in genomics, functional genomics, structural genomics, and proteomics.

Episode link: https://basebybase.com/episodes/echovirus-18-capsid-opening-432

QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-07-23.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited the transcript sections describing E18 structure, FcRn binding and pocket-factor expulsion, endosomal acidification and detachment, in vivo evidence of empty/open capsids, and the genome release mechanism.
- transcript topics: Echovirus 18 capsid structure and pocket factor; FcRn receptor binding and pocket-factor expulsion; Endocytosis and endosomal acidification as uncoating trigger; In vivo evidence: genome-containing particles lack pocket factors; Capsid opening with loss of one to three pentamers; Endosome rupture and cytoplasmic delivery of RNA

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 5
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article_title
- article_journal
- license

Factual Items Audited:
- In vivo, echovirus 18 genome release occurs via capsid opening with loss of one to three pentamers.
- FcRn binding to E18 promotes expulsion of pocket factors, priming the virus for uncoating.
- Genome-containing particles inside infected cells lack pocket factors, suggesting receptor binding induced pocket-factor loss in vivo.
- Acidic endosomal pH detaches the virus from FcRn and triggers genome release; blocking acidification traps particles in endosomes.
- Endosome rupture delivers the genome into the cytoplasm, completing genome delivery.
- In vivo structure resolution of genome-containing particles

QC result: Pass.

Owino BO et al., Proceedings of the National Academy of Sciences - TurboID proximity labeling and proteomics identify KIAP4 as the canonical member of a conserved Adhesion Related NTPase-like Domain (ARND) family that localizes to the Leishmania adhesion plaque. KIAP4 deletion disrupts haptomonad adhesion and prevents stomodeal valve colonization in sand flies. Key terms: Leishmania, adhesion, KIAP4, ARND family, vector colonization.

Study Highlights:
Using TurboID-tagged KIAP3 and mass spectrometry, the authors identified KIAP4 and multiple ARND family paralogs enriched at the adhered flagellum. KIAP4 localizes to the adhesion plaque alongside KIAP3 and accumulates during haptomonad differentiation. KIAP4 deletion severely reduces in vitro adhesion and abolishes stomodeal valve colonization in Lutzomyia longipalpis, while ARND paralogs are conserved and localize to adhered flagella in Trypanosoma congolense. Phylogenetic analysis shows ancient duplications and lineage-specific expansions of the ARND family across kinetoplastids.

Conclusion:
KIAP4 is a foundational adhesion-plaque protein and founding member of a conserved ARND family required for Leishmania haptomonad adhesion and sand fly stomodeal valve colonization, making ARND proteins candidate targets for transmission-blocking strategies.

Music:
Enjoy the music based on this article at the end of the episode.

Article title:
Identification of a conserved gene family with an essential role in
Leishmania
parasite–insect vector adhesion

First author:
Owino BO

Journal:
Proceedings of the National Academy of Sciences

DOI:
10.1073/pnas.2603653123

Reference:
Owino BO, Yanase R, Pruzinovac K, Farr H, Lopez Y, Marron AO, Vaughan S, Volf P, Sunter JD. Identification of a conserved gene family with an essential role in Leishmania parasite–insect vector adhesion. Proc Natl Acad Sci U S A. 2026;123(30):e2603653123. doi:10.1073/pnas.2603653123

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

Support:
Base by Base is independent and ad-free — no sponsors, no paywall. If an episode was worth your time, chip in and keep the papers audited and the original songs coming:
❤️ Support monthly: https://buy.stripe.com/cNifZhclVebvagk2JDgEg01
☕ One-time donation: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00
More at basebybase.com

On PaperCast Base by Base you'll discover the latest in genomics, functional genomics, structural genomics, and proteomics.

Episode link: https://basebybase.com/episodes/kiap4-arnd-leishmania-adhesion

QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-07-23.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited spoken sections covering (1) identification of KIAP4 as the canonical ARND member and its adhesion-plaque localization, (2) TurboID proximity labeling methodology and protein enrichment results, (3) KIAP4 functional analyses including in vitro adhesion and in vivo valve colonization, (4) ARND conservation acros
- transcript topics: KIAP4 and ARND identification in Leishmania; TurboID proximity labeling workflow and enrichment of adhesion-plaque components; Localization of KIAP4 and KIAP3 within the adhesion plaque; KIAP4 knockout effects on haptomonad adhesion and sand fly stomodeal valve colonization; ARND conservation across kinetoplastids (Trypanosoma congolense; T. brucei cross-species data); Inactive Walker A motif in ARND proteins (NTPase-like domains)

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 7
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article_title
- article_journal
- license

Factual Items Audited:
- KIAP4 is the canonical ARND member and localizes to the adhesion plaque.
- ARND gene family is ancient and conserved across kinetoplastids; Trypanosoma congolense paralogs localize to the adhered flagellum.
- ARND domains contain p-loop NTPase-like motifs that lack the Walker A motif, indicating inactive NTPase-like domains.
- TurboID proximity labeling identified KIAP4 and additional ARND family members enriched at the adhered flagellum.
- KIAP4 deletion severely impairs haptomonad adhesion and prevents stomodeal valve colonization in sand flies.
- KIAP4 knockout parasites remain viable and metacyclic forms are produced, but valve colonization is abolished.

QC result: Pass.

Sandin MM et al., Proceedings of the National Academy of Sciences - Molecular clocks and diversification models applied to a 75,975-OTU rDNA dataset, including long-read environmental sequences and 77 fossil calibrations, indicate crown-group eukaryotes diversified steadily from the mid‑Proterozoic with Archaeplastida dominating early diversity. Key terms: eukaryote evolution, Proterozoic diversification, Archaeplastida, molecular clock, environmental sequencing.

Study Highlights:
The study assembled 75,975 nonredundant rDNA OTUs combining long-read environmental metabarcoding and reference sequences and calibrated 32 timetrees with 77 fossil constraints. Molecular dating places LECA at ~1775 Ma and finds most eukaryotic supergroups originating across the Mesoproterozoic. Diversification analyses (ClaDS, BAMM) show steady accumulation of crown-group diversity through the Proterozoic, with Archaeplastida exhibiting an early rapid diversification likely tied to plastid endosymbiosis. Results suggest crown eukaryotes were ecologically and taxonomically diverse long before clear crown-group fossils appear.

Conclusion:
Integrating extensive environmental sequencing with molecular dating and diversification models reveals that crown-group eukaryotes were diversifying steadily from the mid‑Proterozoic, overturning the notion of a biologically stagnant “boring billion” and indicating early ecological interactions and endosymbioses drove diversification.

Music:
Enjoy the music based on this article at the end of the episode.

Article title:
Environmental phylogenetics supports a steady diversification of crown eukaryotes starting from the mid-Proterozoic

First author:
Sandin MM

Journal:
Proceedings of the National Academy of Sciences

DOI:
10.1073/pnas.2600283123

Reference:
Sandin MM, Burki F, Cohen PA, Morlond H (2026) Environmental phylogenetics supports a steady diversification of crown eukaryotes starting from the mid-Proterozoic. PNAS 123(29):e2600283123. doi:10.1073/pnas.2600283123

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

Support:
Base by Base is independent and ad-free — no sponsors, no paywall. If an episode was worth your time, chip in and keep the papers audited and the original songs coming:
❤️ Support monthly: https://buy.stripe.com/cNifZhclVebvagk2JDgEg01
☕ One-time donation: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00
More at basebybase.com

On PaperCast Base by Base you'll discover the latest in genomics, functional genomics, structural genomics, and proteomics.

Episode link: https://basebybase.com/episodes/environmental-phylogenetics-steady-diversification-crown-eukaryotes

QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-07-23.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited transcript segments covering LECA dating and molecular clock; environmental sequencing (OTUs and 18S-28S rDNA); Archaeplastida endosymbiosis and early diversification; Proterozoic diversification dynamics and the 'boring billion' reinterpretation; predator–prey dynamics and fossil evidence; and limitations/samp
- transcript topics: LECA dating and molecular clock; Environmental metabarcoding and OTU dataset (75,975 OTUs); Archaeplastida diversification and plastid endosymbiosis; Proterozoic diversification vs. 'boring billion' narrative; Predation, defense, and ecosystem dynamics (fossil evidence); Sampling limitations and diversification modeling (ClaDS, BAMM)

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 5
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article_title
- article_journal
- license

Factual Items Audited:
- LECA age around 1775 Ma (≈1775 million years ago)
- Archaeplastida rapid early diversification around 1343 Ma
- Diversity inferred from 75,975 OTUs and 77 fossil calibrations underpin dating
- Cyanobacterial endosymbiosis gave rise to plastids in Archaeplastida
- Evidence of predator–prey interactions and biomineralization in late Proterozoic fossils
- Diversification modeled across time with ClaDS and BAMM; sampling fraction ~50–77%

QC result: Pass.

Barna LS et al., Human Genetics and Genomics Advances - We summarize a psychometric validation of the EAGL measure using US adult online samples. The study produced a validated 17-item EAGL-short that captures three core genetic literacy constructs and can be used to assess and target genetic communication and education. Key terms: genetic literacy, EAGL, psychometrics, knowledge comprehension, autism.

Study Highlights:
The authors administered the EAGL across three online US samples (combined N ≈ 2,708) and used exploratory and confirmatory factor analyses to refine the instrument. The final EAGL-short contains 17 items loading on three factors: subjective knowledge, knowledge comprehension, and conceptual (objective) knowledge, with CFA fit indices showing excellent model fit (CFI = 0.996, RMSEA = 0.031, SRMR = 0.080). Regression analyses found numeracy to be the strongest predictor across subscales, a personal connection to autism raised subjective familiarity but not comprehension or conceptual knowledge, and metropolitan vs non-metropolitan status showed no main effects. An interaction between education and connection to autism was observed for knowledge comprehension, highlighting education as a moderator.

Conclusion:
The EAGL-short is a psychometrically sound, 17-item tool that measures subjective knowledge, knowledge comprehension, and conceptual genetic knowledge in US adults; it enables more precise assessment of genetic literacy and the design of targeted educational interventions, though further validation in other languages and settings is recommended.

Music:
Enjoy the music based on this article at the end of the episode.

Article title:
Psychometric validation of the education and assessment of genetic literacy or the EAGL measure

First author:
Barna LS

Journal:
Human Genetics and Genomics Advances

DOI:
10.1016/j.xhgg.2026.100651

Reference:
Barna LS, Liao Y, Wierzbicki MR, Ramírez-Renta GM, Kaphingst KA, Gunter C. Psychometric validation of the education and assessment of genetic literacy or the EAGL measure. Human Genetics and Genomics Advances. 2026;7:100651. doi:10.1016/j.xhgg.2026.100651.

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

Support:
Base by Base is independent and ad-free — no sponsors, no paywall. If an episode was worth your time, chip in and keep the papers audited and the original songs coming:
❤️ Support monthly: https://buy.stripe.com/cNifZhclVebvagk2JDgEg01
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On PaperCast Base by Base you'll discover the latest in genomics, functional genomics, structural genomics, and proteomics.

Episode link: https://basebybase.com/episodes/eagl-psychometric-validation

QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-07-23.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Substantive auditing covered the EAGL-short validation narrative, the three constructs, the autism infographic comprehension exercise, numeracy as predictor, autism connection effects, geography/metropolitan status findings, and the education-autism interaction implications as presented in the transcript.
- transcript topics: EAGL-short three-factor structure; Autism infographic used for knowledge comprehension; Numeracy as predictor of genetic literacy; Autism connection influencing subjective knowledge; Geography/metro status effects on literacy; Education by autism interaction affecting knowledge comprehension

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 7
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article_title
- article_journal
- license

Factual Items Audited:
- Three-factor structure of EAGL-short: subjective knowledge, knowledge comprehension, conceptual knowledge
- Knowledge comprehension tested using an autism infographic model of a complex condition
- Numeracy is the strongest predictor across all three subscales
- Autism connection increases subjective knowledge but not knowledge comprehension or conceptual knowledge
- Metropolitan vs non-metropolitan status shows no significant main effect on literacy
- Education by autism interaction influences knowledge comprehension

QC result: Pass.

Ait Oumelloul M et al., Human Genetics and Genomics Advances - Untargeted plasma metabolomics (1,930 features) in 1,244 participants of the Swiss HIV Cohort Study were paired with genome-wide genotypes to map genetic influences on metabolite levels, test colocalization with eQTLs, and apply Mendelian randomization to probe causal links with aging-related biomarkers and diseases. Key terms: HIV, metabolomics, GWAS, Mendelian randomization, NAT8.

Study Highlights:
The study performed GWAS on 1,930 putative plasma metabolites measured by untargeted mass spectrometry in 1,244 people with HIV and identified 27 metabolites associated with 12 genetic loci, including NAT8, FUT2, PYROXD2, and FADS. Colocalization analyses found that 24 of the 27 metabolite loci overlapped with tissue eQTLs, linking genetic variants to gene expression and metabolite variation. Mendelian randomization using MR-link-2 provided evidence for putative causal relationships, notably genetically higher N-acetylcitrulline associated with lower serum creatinine (protective for kidney function) and chorismate linked to higher cholesterol and triglycerides. Sensitivity analyses across ancestries and sex and partial replication in non-HIV data supported the robustness of key signals.

Conclusion:
Integrating untargeted metabolomics with GWAS, eQTL colocalization, and MR in people with HIV revealed host genetic regulation of plasma metabolites, identified colocalized expression signals, and suggested causal links between specific metabolites and kidney and lipid biomarkers, highlighting targets for follow-up and the utility of multi-omics for precision comorbidity research in this population.

Music:
Enjoy the music based on this article at the end of the episode.

Article title:
Genome-wide association study of untargeted plasma metabolomic profiles identifies host genetic regulation in people with HIV

First author:
Ait Oumelloul M

Journal:
Human Genetics and Genomics Advances

DOI:
10.1016/j.xhgg.2026.100635

Reference:
Ait Oumelloul M, van der Graaf A, Tang S, Thorball CW, Labarile M, Saadat A, Timonina V, Schöpf IC, Wandeler G, Nemeth J, Cavassini M, Calmy A, Schmid P, Stöckle M, Elzi L, Zamboni N, Kouyos RD, Tarr PE, Fellay J; Swiss HIV Cohort Study. Genome-wide association study of untargeted plasma metabolomic profiles identifies host genetic regulation in people with HIV. Human Genetics and Genomics Advances. 2026;7:100635. https://doi.org/10.1016/j.xhgg.2026.100635

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

Support:
Base by Base is independent and ad-free — no sponsors, no paywall. If an episode was worth your time, chip in and keep the papers audited and the original songs coming:
❤️ Support monthly: https://buy.stripe.com/cNifZhclVebvagk2JDgEg01
☕ One-time donation: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00
More at basebybase.com

On PaperCast Base by Base you'll discover the latest in genomics, functional genomics, structural genomics, and proteomics.

Episode link: https://basebybase.com/episodes/genetic-metabolomics-hiv-428

QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-07-23.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited portions include study design and population, untargeted metabolomics, GWAS of metabolites, eQTL colocalization, Mendelian randomization analyses, and key metabolite–gene–disease links (NAT8/N-acetylcitrulline, chorismate, F11/5-HTP), along with limitations and clinical implications discussed in the transcript.
- transcript topics: Untargeted plasma metabolomics in HIV; GWAS of metabolite levels (mQTLs); eQTL colocalization analyses; Mendelian randomization for causal links to kidney and lipid biomarkers; NAT8 and N-acetylcitrulline pathway and kidney function; Chorismate and microbial translocation influencing lipids

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 5
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article_title
- article_journal
- license

Factual Items Audited:
- 1,930 putative metabolites measured in 1,244 participants; 27 metabolites significantly associated with 12 genetic loci
- Key loci include NAT8, FUT2, PYROXD2, and FADS
- 24 of 27 metabolites show colocalization with tissue eQTLs (PP.H4 ≥ 0.8)
- MR identified four metabolite–trait causal associations; N-acetylcitrulline with creatinine; chorismate with cholesterol and triglycerides; 2-O-L-fucopyranosyl-galactose with chole
- N-acetylcitrulline levels inversely associated with creatinine; replication in CLSA for this pair
- F11 variant near F11 associated with 5-hydroxytryptophan in HIV cohort but not observed in general-population cohorts

QC result: Pass.

Simpson RC et al., Trends in Genetics - This forum reviews evidence that host genetic variants associated with metabolic disease often overlap with loci that shape gut microbiome composition and function. Examples include LCT/MCM6 linking Bifidobacterium to reduced T2D risk, defensin locus variants affecting DEFA26 and Akkermansia abundance, and rs7133214 associating with HbA1c. The authors outline mechanisms, analytic tools, and experimental strategies to resolve causality and call for centralized microbiome–genetic resources. Key terms: gut microbiome, genetics, type 2 diabetes, defensins, bile acids.

Study Highlights:
The authors compile microbial GWAS loci and perform phenome-wide scans using the Synteny tool, revealing significant overlaps between microbe-associated SNPs and metabolic traits including obesity, HDL, blood glucose, and T2D. Case studies highlight loci such as LCT/MCM6, defensin genes (DEFA26–Akkermansia), and rs7133214 (methionine pathway) as examples of microbiome-mediated effects. Mechanisms likely include immune-mediated (Paneth cell defensins, NOD2, FUT2) and substrate/metabolite-mediated (lactose metabolism, bile acids, polyamines) pathways. The paper advocates integrated multi-omic studies, Mendelian randomisation, and human–mouse syntenic mapping, and emphasizes the need for a centralized database to enable causal inference.

Conclusion:
Host genetic control of the gut microbiome is widespread and may mediate many genetic links to metabolic disease; resolving causality will require integrated multi-omic datasets, improved causal-mapping tools, standardized databases, and complementary human and controlled mouse studies.

Music:
Enjoy the music based on this article at the end of the episode.

Article title:
The gut microbiome as an effector of metabolic disease gene variants

First author:
Simpson RC

Journal:
Trends in Genetics

DOI:
10.1016/j.tig.2026.03.011

Reference:
Simpson RC, Cutler HB, James DE, Masson SWC. The gut microbiome as an effector of metabolic disease gene variants. Trends in Genetics. 2026;42(7):585-588. https://doi.org/10.1016/j.tig.2026.03.011

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

Support:
Base by Base is independent and ad-free — no sponsors, no paywall. If an episode was worth your time, chip in and keep the papers audited and the original songs coming:
❤️ Support monthly: https://buy.stripe.com/cNifZhclVebvagk2JDgEg01
☕ One-time donation: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00
More at basebybase.com

On PaperCast Base by Base you'll discover the latest in genomics, functional genomics, structural genomics, and proteomics.

Episode link: https://basebybase.com/episodes/genes-gut-microbiome-metabolic-variants

QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-07-23.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Substantively audited portions covering: (1) host genetic regulation of the gut microbiome and immune barrier, (2) specific gene–microbiome examples (LCT/MCM6, defensin locus, TCF7L2), (3) methodological approach (Synteny, CNV/MR concepts), (4) overlaps between microbial SNPs and human metabolic traits (HbA1c, HDL, obe
- transcript topics: Gut microbiome as metabolic organ governed by host genetics; Lactase persistence (LCT/MCM6) and T2D risk via microbial metabolism; Defensin locus variants and Akkermansia muciniphila in mice; TCF7L2's role in Paneth cell development and dysbiosis; Synteny tool, microbial GWAS, and Mendelian randomisation concepts; Overlap of microbial SNPs with human metabolic traits (HbA1c, HDL, obesity)

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 6
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article_title
- article_journal
- license

Factual Items Audited:
- The lactase persistence LCT/MCM6 loci variants increase lactose metabolism and promote Bifidobacterium spp., linked to reduced T2D risk.
- Defensin locus variants increase DEFA26 expression and Akkermansia muciniphila abundance; synthetic DEFA26 recapitulates metabolic benefits in mice.
- SNP rs7133214 strongly associates with HbA1c; linked to microbial methionine salvage pathway; KLHL42 is the nearest human gene.
- 28 phenotypic groups show genome-wide significant associations to microbe-associated SNPs; approximately 16% of these are hematological (monocyte/lymphocyte counts).
- Overlaps between microbiome-associated SNPs and host cholesterol metabolism; involvement of bile acids and FXR signaling in hepatic cholesterol metabolism.
- TCF7L2, Crohn's disease links, and the potential dysbiosis-mediated pathway to insulin resistance.

QC result: Pass.