Base by Base

Gustavo Barra
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Base by Base explores advances in genetics and genomics, with a focus on gene-disease associations, variant interpretation, protein structure, and insights from exome and genome sequencing. Each episode breaks down key studies and their clinical relevance—one base at a time. Powered by AI, Base by Base offers a new way to learn on the go. Special thanks to authors who publish under CC BY 4.0, making open-access science faster to share and easier to explore.

  1. 4 hr ago

    437: Cell villages and Dirichlet modeling map human cell fitness genetics

    Hanson C et al., The American Journal of Human Genetics - Hanson et al. combine pooled multi-donor human neural progenitor cell "villages" with Townlet, a hierarchical Dirichlet regression model, to estimate donor-specific proliferation and treatment responses from Census-seq. They identify 16p11.2 deletion–associated NPC hyperproliferation and nominate common variants near ZFHX3 for proliferation and an ARNT2-linked locus for lead (Pb) sensitivity. Key terms: cell villages, Dirichlet regression, neural progenitor cells, 16p11.2 deletion, lead (Pb) sensitivity. Study Highlights: The authors developed and validated cell villages of 12–39 donor-derived NPC lines and Townlet, a Dirichlet regression framework, to analyze compositional time-series Census-seq data and estimate donor proliferation and treatment effects. Using this system they detected hyperproliferation of NPCs carrying the 16p11.2 deletion, mapped a common variant near ZFHX3 associated with proliferation, and identified ARNT2-linked variants associated with differential sensitivity to lead. Villages preserved donor-intrinsic growth rates while reducing technical variation, and Townlet outperformed standard models in simulations and empirical benchmarks. Conclusion: Pooled multi-donor NPC villages combined with the Townlet Dirichlet model provide a scalable, reproducible platform to map genetic and gene–environment effects on human cell fitness, nominating 16p11.2, ZFHX3, and ARNT2 as contributors to NPC proliferation and Pb sensitivity. Music: Enjoy the music based on this article at the end of the episode. Article title: Cell villages and Dirichlet modeling map human cell fitness genetics First author: Hanson C Journal: The American Journal of Human Genetics DOI: 10.1016/j.ajhg.2026.07.005 Reference: Hanson C., Derebenskiy T., Rodriguez Vega A., et al. Cell villages and Dirichlet modeling map human cell fitness genetics. The American Journal of Human Genetics. 2026;113:1–21. doi:10.1016/j.ajhg.2026.07.005 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/cell-villages-dirichlet-modeling-human-cell-fitness QC: This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-08-09. QC Scope: - article metadata and core scientific claims from the narration - excludes analogies, intro/outro, and music - transcript coverage: Audited the transcript sections describing Townlet and cell villages, validation against array cultures, 16p11.2 deletion hyperproliferation, GWAS identifying ZFHX3-associated proliferation variants, and lead (Pb) resistance modifiers linked to ARNT2; also reviewed environmental exposome implications and limitations di - transcript topics: Cell villages concept and Townlet model; Census-seq and compositional data challenges; Village vs array validation and donor-intrinsic proliferation; 16p11.2 deletion NPC hyperproliferation in villages; GWAS in villages identifying ZFHX3 locus and rs34470044; Lead (Pb) exposure and ARNT2-associated Pb resistance QC Summary: - factual score: 10/10 - metadata score: 10/10 - supported core claims:...

  2. 17 hr ago

    436: KIAP4 and the ARND family: building the Leishmania adhesion plaque

    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 ca...

  3. 2 days ago

    435: E. coli TGT binds two tRNAs — cryo-EM reveals dual engagement

    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 - me...

  4. 3 days ago

    434: High‑coverage genomes recast Japan's prehistoric demography

    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...

  5. 23 Jul

    433: Lactate, HSP90α and the Mitochondrial Switch

    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 claim...

  6. 23 Jul

    432: Echovirus 18: Capsid opening releases the genome

    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...

  7. 23 Jul

    431: KIAP4 and the ARND family: essential proteins for Leishmania–sand fly adhesion

    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: 1...

  8. 23 Jul

    430: Proterozoic Rise: Steady Diversification of Crown Eukaryotes

    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 - met...

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About

Base by Base explores advances in genetics and genomics, with a focus on gene-disease associations, variant interpretation, protein structure, and insights from exome and genome sequencing. Each episode breaks down key studies and their clinical relevance—one base at a time. Powered by AI, Base by Base offers a new way to learn on the go. Special thanks to authors who publish under CC BY 4.0, making open-access science faster to share and easier to explore.

Information

  • Creator
    Gustavo Barra
  • Years Active
    2025 - 2026
  • Episodes
    439
  • Rating
    Clean
  • Copyright
    © Gustavo Barra
  • Show Website
    Base by Base

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