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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

00:19:54

236: XPD translocation and genetic disease etiology

Base by Base ·

2025/12/22

️ Episode 236: XPD translocation and genetic disease etiology In this episode of PaperCast Base by Base, we explore Computational modeling reveals how ATP-driven conformational cycles of the XPD helicase drive directional 5′→3′ translocation on single-stranded DNA and how mutations disrupt this process to cause disease Study Highlights:The authors combined molecular dynamics, partial nudged elastic band path optimization, transition path sampling, and

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00:17:56

235: Maternal H3K9 methyltransferases control aRMAE...

Base by Base ·

2025/12/21

️ Episode 235: Maternal H3K9 methyltransferases control aRMAE in C. elegans In this episode of PaperCast Base by Base, we explore Using dual-color reporters in C. elegans, the study shows maternal H3K9 methyltransferases MET-2 and SET-25 antagonistically regulate autosomal random monoallelic expression initiated in the early embryo Study Highlights:Dual-color fluorescent reporter alleles in C. elegans intestine cells enabled single-cell quantification

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00:17:56

235: Maternal H3K9 methyltransferases control aRMAE...

Base by Base ·

2025/12/21

️ Episode 235: Maternal H3K9 methyltransferases control aRMAE in C. elegans In this episode of PaperCast Base by Base, we explore Using dual-color reporters in C. elegans, the study shows maternal H3K9 methyltransferases MET-2 and SET-25 antagonistically regulate autosomal random monoallelic expression initiated in the early embryo Study Highlights:Dual-color fluorescent reporter alleles in C. elegans intestine cells enabled single-cell quantification of

en-us

00:17:56

234: MTHFR genotype and methionine metabolism predict...

Base by Base ·

2025/12/20

️ Episode 234: MTHFR genotype and methionine metabolism predict COVID-19 severity In this episode of PaperCast Base by Base, we explore IMPACC longitudinal metabolomics and genomics analyses show that disruptions in one‑carbon/methionine metabolism together with MTHFR C677T genotype at hospital admission improve prediction of severe COVID‑19 and long COVID risk Study Highlights:IMPACC profiled plasma metabolites (global and targeted) from over 1,000

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00:18:48

233: Mechanistic basis of NuA3 recognition and H3K14...

Base by Base ·

2025/12/19

️ Episode 233: Mechanistic basis of NuA3 recognition and H3K14 acetylation In this episode of PaperCast Base by Base, we explore Cryo-EM structures of the yeast NuA3 complex reveal how a cooperative Sas3–Nto1 binding cleft recognizes the H3 tail and directs acetylation of H3K14 Study Highlights:The authors report cryo-EM structures of NuA3 in apo, acetyl-CoA-bound, and acetyl-CoA plus H3 tail-bound states at ~3.7, 3.1, and 3.2 Å resolution respectively

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00:18:49

233: Mechanistic basis of NuA3 recognition and H3K14...

Base by Base ·

2025/12/19

️ Episode 233: Mechanistic basis of NuA3 recognition and H3K14 acetylation In this episode of PaperCast Base by Base, we explore Cryo-EM structures of the yeast NuA3 complex reveal how a cooperative Sas3–Nto1 binding cleft recognizes the H3 tail and directs acetylation of H3K14 Study Highlights:The authors report cryo-EM structures of NuA3 in apo, acetyl-CoA-bound, and acetyl-CoA plus H3 tail-bound states at ~3.7, 3.1, and 3.2 Å resolution respectively

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00:17:59

232: Lamin A/C steers fork restart via H3K9me3 and...

Base by Base ·

2025/12/18

️Episode 232: Lamin A/C steers fork restart via H3K9me3 and PARylation In this episode of PaperCast Base by Base, we explore Nucleoplasmic Lamin A/C, together with LAP2α, enforces active replication fork slowing during mild replication stress by promoting local H3K9me3 and ADP-ribosylation to restrain RECQ1-mediated restart and protect genome stability Study Highlights:Lamin A/C dynamically associates with replication factories throughout the nucleus and

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00:17:59

232: Lamin A/C steers fork restart via H3K9me3 and...

Base by Base ·

2025/12/18

️Episode 232: Lamin A/C steers fork restart via H3K9me3 and PARylation In this episode of PaperCast Base by Base, we explore Nucleoplasmic Lamin A/C, together with LAP2α, enforces active replication fork slowing during mild replication stress by promoting local H3K9me3 and ADP-ribosylation to restrain RECQ1-mediated restart and protect genome stability Study Highlights:Lamin A/C dynamically associates with replication factories throughout the nucleus and

en-us

00:17:01

231: Transcription start sites as a germline...

Base by Base ·

2025/12/17

️Episode 231: Transcription start sites as a germline mutational hotspot In this episode of PaperCast Base by Base, we explore This study identifies a pronounced germline mutational hotspot centered on transcription start sites (TSSs) driven in part by early embryonic mosaic variants and transcription-associated DNA damage Study Highlights:Extremely rare variants show a localized excess of non(CpG > TpG) mutations around TSSs extending several hundred

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00:17:01

231: Transcription start sites as a germline...

Base by Base ·

2025/12/17

️Episode 231: Transcription start sites as a germline mutational hotspot In this episode of PaperCast Base by Base, we explore This study identifies a pronounced germline mutational hotspot centered on transcription start sites (TSSs) driven in part by early embryonic mosaic variants and transcription-associated DNA damage Study Highlights:Extremely rare variants show a localized excess of non(CpG > TpG) mutations around TSSs extending several hundred

en-us

00:18:27

230: MIDEAS Y654S hyperactivates MiDAC in a dominant...

Base by Base ·

2025/12/17

️Episode 230: MIDEAS Y654S hyperactivates MiDAC in a dominant neurodevelopmental syndrome In this episode of PaperCast Base by Base, we explore A recurrent de novo MIDEAS p.Tyr654Ser variant disrupts an autoinhibitory loop in the MiDAC complex, increasing HDAC1 deacetylase activity and causing a multisystem neurodevelopmental disorder Study Highlights:Two unrelated probands carry the same de novo heterozygous MIDEAS p.Tyr654Ser variant and present with

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00:18:27

230: MIDEAS Y654S hyperactivates MiDAC in a dominant...

Base by Base ·

2025/12/17

️Episode 230: MIDEAS Y654S hyperactivates MiDAC in a dominant neurodevelopmental syndrome In this episode of PaperCast Base by Base, we explore A recurrent de novo MIDEAS p.Tyr654Ser variant disrupts an autoinhibitory loop in the MiDAC complex, increasing HDAC1 deacetylase activity and causing a multisystem neurodevelopmental disorder Study Highlights:Two unrelated probands carry the same de novo heterozygous MIDEAS p.Tyr654Ser variant and present with

en-us

00:19:55

229: Inhibiting PCBP2 condensates in Alzheimer’s

Base by Base ·

2025/12/15

️ Episode 229: Inhibiting PCBP2 condensates in Alzheimer’s In this episode of PaperCast Base by Base, we explore Elevated PCBP2 forms liquid-like condensates that sequester mitochondrial and RNA-binding proteins, stabilize BACE1 mRNA, and promote amyloid pathology while the small molecule CN-0928 reduces PCBP2 via INTS1 to lower Aβ and improve cognition in AD models Study Highlights:PCBP2 protein is increased in AD patient brains and AD mouse models and

en-us

00:19:55

229: Inhibiting PCBP2 condensates in Alzheimer’s

Base by Base ·

2025/12/15

️Episode 229: Inhibiting PCBP2 condensates in Alzheimer’s In this episode of PaperCast Base by Base, we explore Elevated PCBP2 forms liquid-like condensates that sequester mitochondrial and RNA-binding proteins, stabilize BACE1 mRNA, and promote amyloid pathology while the small molecule CN-0928 reduces PCBP2 via INTS1 to lower Aβ and improve cognition in AD models Study Highlights:PCBP2 protein is increased in AD patient brains and AD mouse models and

en-us

00:18:02

228: Two non-competing H3N2 stem antibodies reveal...

Base by Base ·

2025/12/14

️ Episode 228: Two non-competing H3N2 stem antibodies reveal evolving antigenicity In this episode of PaperCast Base by Base, we explore Structural and functional characterization of two group 2 H3 HA stem antibodies, 2F02 and AG2-G02, shows distinct non-overlapping epitopes, protection in mice, and antigenic changes driven by HA2 position 32 that limit AG2-G02 binding Study Highlights:Cryo-EM structures show 2F02 targets the central stem epitope while

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00:16:21

227: 1q gain enables rescue of aneuploid hESCs during...

Base by Base ·

2025/12/13

️ Episode 227: 1q gain enables rescue of aneuploid hESCs during RPE differentiation In this episode of PaperCast Base by Base, we explore This study shows that spontaneous RPE differentiation eliminates most aneuploid human pluripotent stem cells but permits expansion of cells with chromosome 1q gains when they are co-cultured with wild-type cells Study Highlights:Large-scale single-cell genomics revealed pervasive low-grade mosaicism in genetically

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00:16:09

226: FGF4 protects podocytes in diabetic kidney disease

Base by Base ·

2025/12/12

️ Episode 226: FGF4 protects podocytes in diabetic kidney disease In this episode of PaperCast Base by Base, we explore This study shows that podocyte-derived FGF4 is reduced in DKD and that recombinant FGF4 preserves podocyte survival and glomerular function in diabetic models via FGFR1-AMPK-FOXO1 signaling Study Highlights:FGF4 expression is downregulated in kidneys from DKD patients and diabetic mouse models and localizes predominantly to podocytes

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00:16:09

226: FGF4 protects podocytes in diabetic kidney disease

Base by Base ·

2025/12/12

️ Episode 226: FGF4 protects podocytes in diabetic kidney disease In this episode of PaperCast Base by Base, we explore This study shows that podocyte-derived FGF4 is reduced in DKD and that recombinant FGF4 preserves podocyte survival and glomerular function in diabetic models via FGFR1-AMPK-FOXO1 signaling Study Highlights:FGF4 expression is downregulated in kidneys from DKD patients and diabetic mouse models and localizes predominantly to podocytes

en-us

00:17:13

225: VRK-1 and BAF-1 release meiotic chromosomes

Base by Base ·

2025/12/10

️ Episode 225: VRK-1 and BAF-1 release meiotic chromosomes In this episode of PaperCast Base by Base, we explore VRK-1 phosphorylates BAF-1 to remove chromatin from the nuclear periphery during early meiotic prophase in C. elegans, and failure of this step impairs pairing and synapsis and generates heritable genome lesions Study Highlights:The authors used an auxin-inducible VRK-1 depletion system and genetic perturbations to show that VRK-1

en-us

00:17:13

225: VRK-1 and BAF-1 release meiotic chromosomes

Base by Base ·

2025/12/10

️ Episode 225: VRK-1 and BAF-1 release meiotic chromosomes In this episode of PaperCast Base by Base, we explore VRK-1 phosphorylates BAF-1 to remove chromatin from the nuclear periphery during early meiotic prophase in C. elegans, and failure of this step impairs pairing and synapsis and generates heritable genome lesions Study Highlights:The authors used an auxin-inducible VRK-1 depletion system and genetic perturbations to show that VRK-1

en-us

452 results

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