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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

00:16:20

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

en-us

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

en-us

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

en-us

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

en-us

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

en-us

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

en-us

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,

en-us

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

en-us

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

en-us

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

en-us

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

en-us

00:19:00

251: MuSCs, laminin-α2 and LAMA2 MD

Base by Base ·

2026/01/06

️ Episode 251: MuSCs, laminin-α2 and LAMA2 MD In this episode of PaperCast Base by Base, we explore Activated muscle stem cells express and secrete laminin-α2 to remodel their niche, and loss of MuSC-derived laminin-α2 slows MuSC proliferation and delays regeneration in mouse models and human iPSC-derived precursors Study Highlights:Activated MuSCs upregulate Lama2 and deposit laminin-α2 around proliferating cells during early regeneration. MuSCs from

en-us

00:18:16

250: CIP2A–TOPBP1: Mitotic repair via MiDAS and MMEJ

Base by Base ·

2026/01/05

️ Episode 250: CIP2A–TOPBP1: Mitotic repair via MiDAS and MMEJ In this episode of PaperCast Base by Base, we explore This study shows the CIP2A-TOPBP1 complex coordinates two mitotic double-strand break repair pathways, MiDAS and MMEJ, by recruiting SLX4/SMX components and Polθ to mitotic chromatin. Study Highlights:TOPBP1 BRCT1/2 binds SLX4 phosphorylated at Thr1260, a CDK1-dependent modification that promotes recruitment of SLX4, MUS81 and ERCC1 to

en-us

00:20:40

249: PCM1 links centrosome asymmetry to endosome...

Base by Base ·

2026/01/04

️ Episode 249: PCM1 links centrosome asymmetry to endosome dynamics In this episode of PaperCast Base by Base, we explore In developing neural progenitors PCM1 localizes to the mother centrosome and to Notch ligand-containing endosomes, promoting Par-3/dynein assembly and Rab5-to-Rab11 trafficking to bias posterior-directed endosome segregation and preserve progenitor fate Study Highlights:Pcm1 is asymmetrically enriched at the posterior mother

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00:21:12

248: Disruption of PIKfyve triggers lysosomal repair...

Base by Base ·

2026/01/03

️ Episode 248: Disruption of PIKfyve triggers lysosomal repair and mitochondrial adaptation In this episode of PaperCast Base by Base, we explore Disruption of the PIKfyve/Fig4/Vac14 complex drives ULK1-dependent trafficking of PI4KIIα and ATG9A to lysosomes, elevating lysosomal PI(4)P to promote membrane repair and induce mitochondrial fragmentation with increased respiration Study Highlights:PIKfyve complex disruption or pharmacological inhibition

en-us

00:21:12

248: Disruption of PIKfyve triggers lysosomal repair...

Base by Base ·

2026/01/03

️ Episode 248: Disruption of PIKfyve triggers lysosomal repair and mitochondrial adaptation In this episode of PaperCast Base by Base, we explore Disruption of the PIKfyve/Fig4/Vac14 complex drives ULK1-dependent trafficking of PI4KIIα and ATG9A to lysosomes, elevating lysosomal PI(4)P to promote membrane repair and induce mitochondrial fragmentation with increased respiration Study Highlights:PIKfyve complex disruption or pharmacological inhibition

en-us

452 results

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