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PODCAST

Base by Base

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.

science life sciences

All Episodes

00:19:51

271: Rising EA PGI prediction of educational...

Base by Base ·

2026/01/25

Morris TT et al., PNAS - EA and cognition polygenic indexes (PGIs) in three British birth cohorts show EA PGI associations with years of education increased from 1946–1970 and were strongest in advantaged socioeconomic backgrounds. Study Highlights:Using three nationally representative British birth cohorts born 1946, 1958, and 1970, the authors analyzed polygenic indexes for educational attainment (EA) and cognition. They generated PGIs with

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00:22:00

270: Human Topoisomerase IIIα–RMI1–RMI2 (TRR)...

Base by Base ·

2026/01/25

Spakmana D et al., H., Hickson I. D., Peterman E. J. G., Wuite G. J. L., King G. A. Mechanistic basis for relaxation of DNA supercoils by human topoisomerase IIIα–RMI1–RMI2. Proc. Natl. Acad. Sci. U.S.A - Optical tweezers and fluorescence imaging show human Topoisomerase IIIα–RMI1–RMI2 (TRR) processively relaxes highly negatively supercoiled DNA faster than PICH loops. Study Highlights:Using torsionally constrained end-closed λ-DNA in a multichannel flow

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00:20:45

269: Mlh1–Pms1 endonuclease creates single-strand...

Base by Base ·

2026/01/24

Palacio T et al., PNAS - Reconstituted Saccharomyces cerevisiae mismatch repair shows the Mlh1–Pms1 endonuclease directly generates single-strand gaps to excise mispairs independent of Exo1 and Rad27. Study Highlights:We reconstituted Saccharomyces cerevisiae mismatch repair with purified Msh2–Msh6 or Msh2–Msh3, Mlh1–Pms1, PCNA, RFC, RPA, and DNA polymerases and analyzed products by restriction mapping, Mung Bean nuclease, electron microscopy, and

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00:22:05

268: M493I in human β-cardiac myosin: SRX disruption,...

Base by Base ·

2026/01/23

Cail RC et al., PNAS - Recombinant human β-cardiac myosin M493I studied by optical trapping and stopped-flow kinetics disrupts the super-relaxed state and increases actin attachment and contractile force. Study Highlights:System: recombinant human β-cardiac heavy meromyosin (cHMM) expressed in C2C12 cells. Methods: ensemble actin gliding, stopped-flow kinetics, NADH ATPase, mantATP single-turnover, and single-molecule three-bead optical trap assays. Main

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00:22:05

268: M493I in human β-cardiac myosin: SRX disruption,...

Base by Base ·

2026/01/23

Cail RC et al., PNAS - Recombinant human β-cardiac myosin M493I studied by optical trapping and stopped-flow kinetics disrupts the super-relaxed state and increases actin attachment and contractile force. Study Highlights:System: recombinant human β-cardiac heavy meromyosin (cHMM) expressed in C2C12 cells. Methods: ensemble actin gliding, stopped-flow kinetics, NADH ATPase, mantATP single-turnover, and single-molecule three-bead optical trap assays. Main

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00:21:20

267: DNA base-pair opening modes and soliton-like...

Base by Base ·

2026/01/22

Englander SW et al., PNAS - Hydrogen exchange (H-T and NMR H-H) on DNA and RNA reveals two distinct base-pair opening modes: single-base microsecond openings and multi-base millisecond soliton-like loops. Study Highlights:Systems studied include long polynucleotides (DNA, duplex RNA, synthetic long duplexes) and short oligonucleotides; key methods are H-T (tritium) exchange, stopped-flow H-D, and NMR H-H (water relaxation) measurements. H-T exchange of

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00:21:20

267: DNA base-pair opening modes and soliton-like...

Base by Base ·

2026/01/22

Englander SW et al., PNAS - Hydrogen exchange (H-T and NMR H-H) on DNA and RNA reveals two distinct base-pair opening modes: single-base microsecond openings and multi-base millisecond soliton-like loops. Study Highlights:Systems studied include long polynucleotides (DNA, duplex RNA, synthetic long duplexes) and short oligonucleotides; key methods are H-T (tritium) exchange, stopped-flow H-D, and NMR H-H (water relaxation) measurements. H-T exchange of

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00:17:03

266: TOP1α and TOP3β Differentially Regulate HPV31...

Base by Base ·

2026/01/21

Vatsa A et al., PNAS - In HPV31-positive keratinocytes (CIN612), TOP1α and TOP3β are upregulated and required for viral transcription and replication, acting via distinct effects on R-loop accumulation and topoisomerase-mediated DNA breaks. Study Highlights:Using HPV31-positive CIN612 cells and primary HFK controls, the authors applied ChIP, RADAR, DRIP, alkaline COMET, RNA-seq, and shRNA knockdown to map topoisomerase binding and function. They found

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00:17:03

266: TOP1α and TOP3β Differentially Regulate HPV31...

Base by Base ·

2026/01/21

Vatsa A et al., PNAS - In HPV31-positive keratinocytes (CIN612), TOP1α and TOP3β are upregulated and required for viral transcription and replication, acting via distinct effects on R-loop accumulation and topoisomerase-mediated DNA breaks. Study Highlights:Using HPV31-positive CIN612 cells and primary HFK controls, the authors applied ChIP, RADAR, DRIP, alkaline COMET, RNA-seq, and shRNA knockdown to map topoisomerase binding and function. They found

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00:17:51

265: ANTSR lncRNA and the conserved multiallelic...

Base by Base ·

2026/01/20

Yu C et al., Proc. Natl. Acad. Sci. U.S.A - Genetic mapping and comparative genomics show the lncRNA ANTSR multiallelic locus in Aculeata directs female development via heterozygosity despite lacking sequence homology. Study Highlights:The study analyzed 41 hymenopteran genomes and performed whole-genome resequencing and genetic mapping in Bombus terrestris and Vespa velutina nigrithorax to locate the sex-determining region. The ANTSR locus is a

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00:17:51

265: ANTSR lncRNA and the conserved multiallelic...

Base by Base ·

2026/01/20

Yu C et al., Proc. Natl. Acad. Sci. U.S.A - Genetic mapping and comparative genomics show the lncRNA ANTSR multiallelic locus in Aculeata directs female development via heterozygosity despite lacking sequence homology. Study Highlights:The study analyzed 41 hymenopteran genomes and performed whole-genome resequencing and genetic mapping in Bombus terrestris and Vespa velutina nigrithorax to locate the sex-determining region. The ANTSR locus is a

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00:19:44

264: Single-TF rejuvenation: EZH2, E2F3, STAT3, ZFX...

Base by Base ·

2026/01/19

Sengstack J et al., Proc. Natl. Acad. Sci. U.S.A - TRDP with Perturb-seq in human fibroblasts found that manipulating TFs (EZH2, E2F3, STAT3, ZFX) reversed aging hallmarks, and EZH2 overexpression rejuvenated aged mouse livers. Study Highlights:The study used passaged human neonatal dermal fibroblasts and aged mouse liver as model systems and applied the Transcriptional Rejuvenation Discovery Platform (TRDP) with Perturb-seq and CRISPRa/CRISPRi screens

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00:20:24

263: Bifacial γPNA triplets target rCUG repeats and...

Base by Base ·

2026/01/18

Perera J et al., R., Thadke S. A., Thrikawala S. W., Wilson W. D., Tan K. W. R., Chand N. Z. W., Phan A. T., Ly D. H., et al. A pothole-filling strategy for selective targeting of rCUG-repeats associated with myotonic dystrophy type 1. Proc. Natl. Acad. Sci. U.S.A - Gamma-PNA triplet ligands with Janus bases selectively bind expanded rCUG repeats, displace MBNL1, and show length-dependent cooperativity with partial splicing rescue. Study Highlights:The

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00:21:40

262: Human Langerhans cells reprogrammed by tick...

Base by Base ·

2026/01/17

Strobl et al., & Stary, G. Human epidermal Langerhans cells induce tolerance and hamper T cell function upon tick-borne pathogen transmission. Nature Communications - Human epidermal Langerhans cells exposed to Ixodes ricinus tick saliva and Borrelia burgdorferi adopt a tolerogenic state with CXCR4/CCR7-driven emigration that impairs T cell priming. Study Highlights:The study uses clinical human tick bite biopsies, an ex vivo human skin tick bite

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00:21:40

262: Human Langerhans cells reprogrammed by tick...

Base by Base ·

2026/01/17

Strobl et al., & Stary, G. Human epidermal Langerhans cells induce tolerance and hamper T cell function upon tick-borne pathogen transmission. Nature Communications - Human epidermal Langerhans cells exposed to Ixodes ricinus tick saliva and Borrelia burgdorferi adopt a tolerogenic state with CXCR4/CCR7-driven emigration that impairs T cell priming. Study Highlights:The study uses clinical human tick bite biopsies, an ex vivo human skin tick bite

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00:16:20

261: MHz-XPCS reveals anomalous ferritin diffusion...

Base by Base ·

2026/01/16

Girelli et al., Coherent X-rays reveal anomalous molecular diffusion and cage effects in crowded protein solutions. Nat Commun ( - MHz-XPCS of ferritin solutions at EuXFEL shows anomalous, cage-trapped protein diffusion with reduced long-time transport and ~1.2 nm rattling at high concentration. Study Highlights:The study probes crowded ferritin solutions using megahertz X-ray Photon Correlation Spectroscopy (MHz-XPCS) at EuXFEL combined with SAXS and

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00:16:20

261: MHz-XPCS reveals anomalous ferritin diffusion...

Base by Base ·

2026/01/16

Girelli et al., Coherent X-rays reveal anomalous molecular diffusion and cage effects in crowded protein solutions. Nat Commun ( - MHz-XPCS of ferritin solutions at EuXFEL shows anomalous, cage-trapped protein diffusion with reduced long-time transport and ~1.2 nm rattling at high concentration. Study Highlights:The study probes crowded ferritin solutions using megahertz X-ray Photon Correlation Spectroscopy (MHz-XPCS) at EuXFEL combined with SAXS and

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00:16:09

260: TSS hypermutability in human germline linked to...

Base by Base ·

2026/01/15

Cortés Guzmán M et al., Nat Commun - Human germline transcription start sites show a hotspot of non-CpG variants driven by the early embryonic mosaicism, RNAP II stalling, R-loops and mitotic DSBs. Study Highlights:The authors analysed extremely rare variants from gnomAD and UK Biobank, de novo mutations from family sequencing, mosaic variant catalogs, and pan-cancer somatic data to map mutation density around transcription start sites in humans. They

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00:16:09

260: TSS hypermutability in human germline linked to...

Base by Base ·

2026/01/15

Cortés Guzmán M et al., Nat Commun - Human germline transcription start sites show a hotspot of non-CpG variants driven by the early embryonic mosaicism, RNAP II stalling, R-loops and mitotic DSBs. Study Highlights:The authors analysed extremely rare variants from gnomAD and UK Biobank, de novo mutations from family sequencing, mosaic variant catalogs, and pan-cancer somatic data to map mutation density around transcription start sites in humans. They

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00:17:49

259: Ku filaments that hold DNA together

Base by Base ·

2026/01/14

Zahid S et al., Nat Commun - Cryo-EM and biophysical analyses show Mycobacterium tuberculosis Ku assembles into DNA-bound oligomeric filaments that synapse DNA ends and are required for survival under DNA-damaging conditions. Study Highlights:Deletion of ku in M. smegmatis causes marked survival defects after methyl methanesulfonate exposure and desiccation that are rescued by complementation. Cryo-EM structures of apo-Ku-Mtb (4.04 Å) and DNA-bound

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448 results

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