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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

00:17:51

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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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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00:17:09

258: Correcting GC bias in metagenomes

Base by Base ·

2026/01/13

Holcik L et al., Genomic GC bias correction improves species abundance estimation from metagenomic data. Nature Communications - GuaCAMOLE is an alignment-free algorithm that estimates and removes genomic GC-content-dependent sequencing bias to produce more accurate species abundance estimates from single metagenomic samples. Key terms: GC bias, metagenomics, species abundance, GuaCAMOLE, colorectal cancer. Study Highlights:GuaCAMOLE combines

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00:18:05

257: PSMC5: proteasomes, immunity and neurodevelopment

Base by Base ·

2026/01/12

Küry S et al., Nat Commun - This study describes 26 distinct PSMC5 variants in 44 individuals and demonstrates that PSMC5 loss impairs proteasome function, driving proteotoxic stress, mitochondrial and lipid dysregulation, sterile type I interferon activation, and neurodevelopmental deficits. Key terms: PSMC5, proteasome, neurodevelopment, interferon, mitophagy. Study Highlights:Twenty-six distinct PSMC5 variants were identified in 44 affected

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00:18:05

257: PSMC5: proteasomes, immunity and neurodevelopment

Base by Base ·

2026/01/12

Küry S et al., Nat Commun - This study describes 26 distinct PSMC5 variants in 44 individuals and demonstrates that PSMC5 loss impairs proteasome function, driving proteotoxic stress, mitochondrial and lipid dysregulation, sterile type I interferon activation, and neurodevelopmental deficits. Key terms: PSMC5, proteasome, neurodevelopment, interferon, mitophagy. Study Highlights:Twenty-six distinct PSMC5 variants were identified in 44 affected

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00:18:52

256: Compartmental control of VSG silencing

Base by Base ·

2026/01/11

Antunes et al., Chromosome compartment assembly is essential for subtelomeric gene silencing in trypanosomes. Nat Commun ( - The study shows that spatial segregation of core and subtelomeric chromosome compartments, demarcated by protein-rich boundaries and controlled by a phosphoinositide regulator, is required to silence subtelomeric VSG genes. Key terms: RAP1, PIP5Pase, VSG, Hi-C, chromatin. Study Highlights:Hi-C and Pore-C reveal that T. brucei

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00:19:08

255: Lipids, Ions and the AE1 Elevator

Base by Base ·

2026/01/10

Chen T et al., Nat Commun - Cryo-EM structures, uptake assays, and molecular dynamics show that PIP2 lipids bind at the AE1 dimer interface and inhibit the OF⇌IF conformational transition while substrate binding lowers the transition barrier. Key terms: AE1, PIP2, bicarbonate transport, cryo-EM, molecular dynamics. Study Highlights:Three high-resolution cryo-EM states were solved: two inward-facing (IF1, IF2) and one outward-facing (OF). Proteoliposome

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00:19:52

254: Rescuing the replisome at a nick

Base by Base ·

2026/01/09

Winterhalter et al., Rescuing the bacterial replisome at a nick requires recombinational repair and helicase reloading. Nat Commun ( - Cas9 nickases in Bacillus subtilis show that single-strand nicks in either template strand arrest DNA replication, create single-end double-strand breaks, and require homologous recombination plus PriA-dependent helicase reloading for replication restart. Key terms: DNA replication, recombinational repair, AddAB, PriA,

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00:20:26

253: Nap1 and histone acetylation tune chromatin...

Base by Base ·

2026/01/08

Gao J et al., Nat Commun - H4 tail lysine residues drive liquid-liquid phase separation of 12‑mer nucleosome arrays, while H3 tail acetylation and the histone chaperone Nap1 increase internal dynamics and lower droplet viscosity. Key terms: Nap1, H3 acetylation, H4 acetylation, liquid-liquid phase separation, nucleosome arrays. Study Highlights:H4 tail lysine residues are the primary drivers of nucleosome array phase separation, and H4-tail acetylation

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00:20:26

253: Nap1 and histone acetylation tune chromatin...

Base by Base ·

2026/01/08

Gao J et al., Nat Commun - H4 tail lysine residues drive liquid-liquid phase separation of 12‑mer nucleosome arrays, while H3 tail acetylation and the histone chaperone Nap1 increase internal dynamics and lower droplet viscosity. Key terms: Nap1, H3 acetylation, H4 acetylation, liquid-liquid phase separation, nucleosome arrays. Study Highlights:H4 tail lysine residues are the primary drivers of nucleosome array phase separation, and H4-tail acetylation

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00:18:13

252: Keratinocytes to cSCC: genetic steps

Base by Base ·

2026/01/07

️ Episode 252: Keratinocytes to cSCC: genetic steps In this episode of PaperCast Base by Base, we explore Single-cell and spatial multi-omic profiling maps the genetic and transcriptional changes from normal keratinocytes through actinic keratoses to invasive cutaneous squamous cell carcinoma Study Highlights:Single-cell genotyping of 137 keratinocytes revealed most cells have low mutation burdens (median 1.14 mut/Mb) while keratinocytes with TP53 or

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418 results

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