Best Mechanist Podcasts (2025)

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233: Mechanistic basis of NuA3 recognition and H3K14 acetylation 18:48

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7d ago18:48

18:48

️ 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,…

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239: Genomic Adaptations of the Svalbard Reindeer 19:21

12h ago19:21

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️ Episode 239: Genomic Adaptations of the Svalbard Reindeer In this episode of PaperCast Base by Base, we explore Comparative whole-genome analyses identify 150 differentiated genomic regions and candidate genes linked to fat metabolism, energy conservation, cold tolerance, reduced body size, fur morphology, and circadian rhythm that likely underpi…

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238: Germline polymorphisms shape antibody light chain repertoires 18:14

1d ago18:14

18:14

️ Episode 238: Germline polymorphisms shape antibody light chain repertoires In this episode of PaperCast Base by Base, we explore Long-read sequencing of IGK and IGL paired with AIRR-seq shows that common germline SNVs, SVs, and alleles drive inter-individual differences in light chain gene usage and CDR3 properties Study Highlights: The authors c…

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237: Tracing enteric pathogens in Africa with metagenomics and WGS 20:00

3d ago20:00

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️ Episode 237: Tracing enteric pathogens in Africa with metagenomics and WGS In this episode of PaperCast Base by Base, we explore This study combines whole-genome sequencing and metagenomics to map the diversity, abundance, and genomic relationships of enteric foodborne pathogens across human, animal, food and environmental samples in four African…

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236: XPD translocation and genetic disease etiology 19:54

4d ago19:54

19:54

️ 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…

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235: Maternal H3K9 methyltransferases control aRMAE in C. elegans 17:56

5d ago17:56

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️ 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…

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234: MTHFR genotype and methionine metabolism predict COVID-19 severity 20:27

6d ago20:27

20:27

️ 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 lo…

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Guidelines for Diet-induced Models of Cardiometabolic Syndrome 17:35

6d ago17:35

17:35

In our latest episode, Deputy Editor Dr. Zam Kassiri (University of Alberta) interviews authors Dr. German González (Pontificia Universidad Católica Argentina), Dr. Rebecca Ritchie (Monash University), Dr. Pooneh Bagher (University of Nebraska Medical Center), and Dr. Hiroe Toba (Kyoto Pharmaceutical University) about the latest Guidelines in Cardi…

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232: Lamin A/C steers fork restart via H3K9me3 and PARylation 17:58

8d ago17:58

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️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 stabi…

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231: Transcription start sites as a germline mutational hotspot 17:01

8d ago17:01

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️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: Extreme…

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230: MIDEAS Y654S hyperactivates MiDAC in a dominant neurodevelopmental syndrome 18:27

9d ago18:27

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️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 Highlig…

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229: Inhibiting PCBP2 condensates in Alzheimer’s 19:55

11d ago19:55

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️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 cogni…

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228: Two non-competing H3N2 stem antibodies reveal evolving antigenicity 18:02

12d ago18:02

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️ 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 …

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227: 1q gain enables rescue of aneuploid hESCs during RPE differentiation 16:21

13d ago16:21

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️ 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 …

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226: FGF4 protects podocytes in diabetic kidney disease 16:09

14d ago16:09

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️ 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 dow…

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225: VRK-1 and BAF-1 release meiotic chromosomes 17:13

15d ago17:13

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️ 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 aut…

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224: AntennAlive — wireless in-body sensing with engineered bacteria 18:41

15d ago18:41

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️ Episode 224: AntennAlive — wireless in-body sensing with engineered bacteria In this episode of PaperCast Base by Base, we explore A bio-hybrid, battery-free implant converts engineered bacterial activity into microwave backscatter signals by controlled degradation of a biodegradable antenna Study Highlights: The AntennAlive system uses a magnesi…

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223: Torsion Regulates DNA Replication Stalling and Restart 16:26

17d ago16:26

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️ Episode 223: Torsion Regulates DNA Replication Stalling and Restart In this episode of PaperCast Base by Base, we explore New single-molecule angular optical trap assays reveal that DNA torsion directly controls T7 replisome stalling and reactivation Study Highlights: A high-resolution, label-free angular optical trap (AOT) assay was developed to…

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222: snaR-A hijacks splicing to drive proliferation 17:57

18d ago17:57

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️ Episode 222: snaR-A hijacks splicing to drive proliferation In this episode of PaperCast Base by Base, we explore This episode examines how the cancer-associated Pol III transcript snaR-A binds core splicing factors, localizes near nuclear speckles, perturbs U2-dependent splicing to increase intron retention, and promotes cell proliferation linke…

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221: Allele-resolved nanopore tour of the human placental methylome 20:23

19d ago20:23

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️ Episode 221: Allele-resolved nanopore tour of the human placental methylome In this episode of PaperCast Base by Base, we explore Using phased long-read nanopore and short-read sequencing across eight trios, the study maps allele-specific DNA methylation and transcription in female human placentas, identifies hundreds of DMRs and novel imprinted …

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220: The AML cellular state space reveals NPM1 immune evasion subtypes 15:48

20d ago15:48

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️Episode 220: The AML cellular state space reveals NPM1 immune evasion subtypes In this episode of PaperCast Base by Base, we explore Single-cell and bulk sequencing of 120 AML cases reveal two NPM1-mutated subtypes with distinct immune evasion mechanisms and divergent responses to hematopoietic stem cell transplantation Study Highlights: Bulk RNA-…

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219: Multi-omic mapping of lipid dysregulation in Parkinson’s brain 16:41

21d ago16:41

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️Episode 219: Multi-omic mapping of lipid dysregulation in Parkinson’s brain In this episode of PaperCast Base by Base, we explore Targeted multi-region lipidomics with proteomic and mitochondrial data reveals region- and stage-specific lipid alterations in Parkinson’s disease that converge on mitochondrial dysfunction Study Highlights: The study q…

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218: SIM1 and the multi-ancestry genomics of erectile dysfunction 19:37

22d ago19:37

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️Episode 218: SIM1 and the multi-ancestry genomics of erectile dysfunction In this episode of PaperCast Base by Base, we explore A large multi-ancestry GWAS meta-analysis identifies a dominant SIM1-linked locus and multiple genetic connections between electronic health record-defined erectile dysfunction and cardiometabolic, psychiatric, and substa…

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217: Multiscale triads of meiotic crossover patterning 17:47

23d ago17:47

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️Episode 217: Multiscale triads of meiotic crossover patterning In this episode of PaperCast Base by Base, we explore FFT and inverse-FFT analysis of Zip3/Zip2, Hop1 and Zip1 on yeast pachytene chromosomes reveals two interdigitated tiers of evenly spaced protein triads that correspond to canonical and minority crossovers and are differentially reg…

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216: 53BP1-RIF1 and DNA-PKcs: distinct interactions in chromosomal break repair 18:27

24d ago18:27

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️ Episode 216: 53BP1-RIF1 and DNA-PKcs: distinct interactions in chromosomal break repair In this episode of PaperCast Base by Base, we explore This episode reviews a study showing that 53BP1-RIF1 and DNA-PKcs have different genetic relationships across blunt end joining, deletion patterns, HDR, and radiosensitivity Study Highlights: Using EJ7-GFP …

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215: Protein Set Transformer for high-diversity viromics 20:07

25d ago20:07

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️ Episode 215: Protein Set Transformer for high-diversity viromics In this episode of PaperCast Base by Base, we explore Protein Set Transformer (PST) is a protein-based genome language model that represents genomes as sets of proteins to improve genome and protein representations across diverse viral datasets Study Highlights: PST embeds proteins …

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214: PI(4,5)P2 Asymmetry Enables Rapid FGF2 Secretion 18:21

25d ago18:21

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️ Episode 214: PI(4,5)P2 Asymmetry Enables Rapid FGF2 Secretion In this episode of PaperCast Base by Base, we explore This study shows that an asymmetric transbilayer distribution of PI(4,5)P2 lowers the energy barrier for lipidic pore formation and accelerates unconventional secretion of Fibroblast Growth Factor 2 Study Highlights: The authors gen…

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213: BRAIN-MAGNET: a functional atlas for non-coding variants 20:29

26d ago20:29

20:29

️ Episode 213: BRAIN-MAGNET: a functional atlas for non-coding variants In this episode of PaperCast Base by Base, we explore BRAIN-MAGNET couples a ChIP-STARR-seq atlas of 148,198 neural regulatory elements with a validated convolutional neural network to predict enhancer activity and prioritize disease-relevant non-coding variants Study Highlight…

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212: Zonal control of mutant β-catenin tumorigenesis 16:47

28d ago16:47

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️ Episode 212: Zonal control of mutant β-catenin tumorigenesis This study shows that hepatic zonation determines whether mutant β-catenin drives proliferation and liver cancer by forcing differentiation to a non-permissive zone 3 fate or, when reversed, enabling MAPK- and mTOR-dependent growth Study Highlights: β-catenin exon 3 mutations cooperate …

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211: Retention Elements in Cancer Cells 19:30

29d ago19:30

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️ Episode 211: Retention Elements in Cancer Cells In this episode of PaperCast Base by Base, we explore the discovery of genetic elements that promote the retention of extrachromosomal DNA (ecDNA) in cancer cells, enhancing their survival and evolution. Study Highlights: Researchers identified a family of genomic elements known as retention element…

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210: Tumour-Reactive CD8 T Cell Clusters in Human Melanoma 18:45

30d ago18:45

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️ Episode 210: Tumour-Reactive CD8 T Cell Clusters in Human Melanoma In this episode of PaperCast Base by Base, we explore how tumour-reactive CD8 T cells organize into stable clusters with melanoma cells and antigen-presenting cells, and how these structures can be isolated from patient samples to boost anti-tumour immunity. Study Highlights: The …

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209: PERT: Prime Editing tRNAs for Nonsense Mutations 16:54

1M ago16:54

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️ Episode 209: PERT: Prime Editing tRNAs for Nonsense Mutations In this episode of PaperCast Base by Base, we explore how prime editing can reprogram endogenous tRNAs into potent suppressor tRNAs, enabling a single therapeutic strategy to rescue many different genetic diseases caused by premature stop codons. Study Highlights: The authors introduce…

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Arrhythpy 28:01

1M ago28:01

28:01

Why is a broad approach that works with iPSC-derived cardiomyocytes so important to understanding molecular mechanisms underlying calcium homeostasis and arrhythmias? In this episode, Associate Editor Dr. Petra Kleinbongard (University of Duisburg-Essen) interviews author Dr. Katrin Streckfuss-Bömeke (University Medical Center Göttingen) and expert…

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208: ZAK, Collided Ribosomes, and the Stress Switch 15:55

1M ago15:55

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️ Episode 208: ZAK, Collided Ribosomes, and the Stress Switch In this episode of PaperCast Base by Base, we explore how collided ribosomes activate the MAP3K ZAK to drive the ribotoxic stress response and shape cell fate decisions under translational stress. Study Highlights: Using biochemistry, cryo-electron microscopy and crosslinking-based RNA m…

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207: Semantic Design of de novo Genes with Evo 15:05

1M ago15:05

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️ Episode 207: Semantic Design of de novo Genes with Evo In this episode of PaperCast Base by Base, we explore how a genomic language model called Evo can use genomic context to design entirely new DNA sequences that encode functional genes and multi-component defence systems. Study Highlights: Researchers trained the Evo genomic language model on …

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206: Wild Birds and the North American H5N1 Epizootic 17:17

1M ago17:17

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️ Episode 206: Wild Birds and the North American H5N1 Epizootic In this episode of PaperCast Base by Base, we explore how wild migratory birds have shaped the ecology and spread of the 2021–2023 highly pathogenic H5N1 epizootic across North America, and what this means for wildlife conservation and poultry health. Study Highlights: Using 1,818 haem…

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205: Ancient RNA Expression Profiles from the Woolly Mammoth 17:19

1M ago17:19

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️ Episode 205: Ancient RNA Expression Profiles from the Woolly Mammoth In this episode of PaperCast Base by Base, we explore how ancient RNA preserved in permafrost can reveal tissue-specific gene expression and regulatory dynamics in the extinct woolly mammoth. Study Highlights: Researchers analyzed skeletal muscle and skin from ten Late Pleistoce…

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204: StealTHY CRISPR: Revealing Hidden Metastasis Regulators 16:39

1M ago16:39

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️ Episode 204: StealTHY CRISPR: Revealing Hidden Metastasis Regulators In this episode of PaperCast Base by Base, we explore how the StealTHY CRISPR platform sidesteps Cas9 immunogenicity to uncover metastasis drivers in immunocompetent and humanized cancer models. Study Highlights: Researchers show that standard CRISPR-Cas9 tools and xenogeneic re…

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203: Divergent Evolutionary Dynamics of Benign and Malignant Tumors 18:08

1M ago18:08

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️ Episode 203: Divergent Evolutionary Dynamics of Benign and Malignant Tumors In this episode of PaperCast Base by Base, we explore how benign and malignant tumors follow different evolutionary trajectories across birds and mammals, and what this reveals about cancer defenses across the tree of life. Study Highlights: The authors combine necropsy d…

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202: Stereo-seq V2: Spatial Total RNA Mapping in FFPE Tissues 17:08

1M ago17:08

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️ Episode 202: Stereo-seq V2: Spatial Total RNA Mapping in FFPE Tissues In this episode of PaperCast Base by Base, we explore how Stereo-seq V2 delivers high-resolution spatial mapping of total RNA in FFPE samples, from mouse brain to breast cancer and tuberculosis lung tissue. Study Highlights: The authors introduce Stereo-seq V2, a random-priming…

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Episode 318: Adhesive Capsulitis of the Shoulder 38:21

1M ago38:21

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Drs Tucker and Lin discuss Adhesive Capsulitis of the Shoulder .By AANA

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201: Sex, Smoking, and Somatic Selection in the Bladder 14:52

1M ago14:52

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️ Episode 201: Sex, Smoking, and Somatic Selection in the Bladder In this episode of PaperCast Base by Base, we explore how ultradeep duplex DNA sequencing of normal human bladder tissue reveals sex- and smoking-related biases in the selection of somatic mutations and cancer driver clones. Study Highlights: Researchers applied ultradeep duplex DNA …

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200: Sperm Sequencing Reveals Extensive Positive Selection in the Male Germline 18:48

1M ago18:48

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️ Episode 200: Sperm Sequencing Reveals Extensive Positive Selection in the Male Germline In this episode of PaperCast Base by Base, we explore how ultra-accurate duplex sequencing of human sperm reveals widespread positive selection in the male germline and its consequences for mutation burden and disease risk in offspring. Study Highlights: This …

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199: PLD4 Deficiency and Lupus: When Nuclease Failure Ignites Autoimmunity 13:57

1M ago13:57

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️ Episode 199: PLD4 Deficiency and Lupus: When Nuclease Failure Ignites Autoimmunity In this episode of PaperCast Base by Base, we explore how loss-of-function mutations in the endolysosomal exonuclease PLD4 cause a monogenic form of systemic lupus erythematosus, reshaping our understanding of nucleic acid sensing and interferon-driven autoimmunity…

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Sex Differences and Cardioprotective Effects of B-Vitamins 19:48

1M ago19:48

19:48

What is the main driver of sex differences in heart failure with reduced ejection fraction (HFrEF)? In our latest episode, Associate Editor Dr. Petra Kleinbongard (University of Duisburg-Essen) interviews lead author Dr. Matthieu Ruiz (Montreal Heart Institute) and expert Dr. Catherine Mounier (Université du Québec à Montréal) about the new study b…

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198: Mechanical Confinement and the Shape-Shifting Life of Melanoma Cells 15:47

1M ago15:47

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️ Episode 198: Mechanical Confinement and the Shape-Shifting Life of Melanoma Cells In this episode of PaperCast Base by Base, we explore how physical forces in the tumor microenvironment can push melanoma cells to switch from a pigment-producing, proliferative state into an invasive, drug-tolerant one, focusing on new work that links mechanical co…

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197: Somatic Mutation and Selection at Population Scale 15:11

1M ago15:11

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️ Episode 197: Somatic Mutation and Selection at Population Scale In this episode of PaperCast Base by Base, we explore how ultra-accurate NanoSeq duplex sequencing reveals the hidden landscape of somatic mutations and clonal selection across blood and oral epithelium in over a thousand adults. Study Highlights: This study introduces improved whole…

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196: Impact of Chromatin Accessibility QTLs Across Immune Contexts 16:37

1M ago16:37

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️ Episode 196: Impact of Chromatin Accessibility QTLs Across Immune Contexts In this episode of PaperCast Base by Base, we explore how single-cell chromatin accessibility QTLs (caQTLs) reshape the interpretation of immune disease genetics by mapping regulatory variation across major immune cell types and disease-relevant states. Study Highlights: T…

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195: Tiny Shields: Lymphoid Microglia in Alzheimer’s Disease 18:22

1M ago18:22

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️ Episode 195: Tiny Shields: Lymphoid Microglia in Alzheimer’s Disease In this episode of PaperCast Base by Base, we explore how a subset of brain immune cells adopts a lymphoid-like program that helps contain inflammation and protect neural circuits in Alzheimer’s disease models. Study Highlights: Using mouse models of amyloid pathology and human …

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Mad Hatter - Echoes of Chaos 1:30:19

1M ago1:30:19

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In a palace of shadows and traps, chaos is an art form—and the Mad Hatter is its maestro. Once a court jester, now a psychotic genius of mayhem, he thrives in the deadly game set by the ruthless Queen. Her inner sanctum is a labyrinth of mechanical horrors: spiked floors, swinging pendulums, venomous contraptions, and mirrored halls designed to bre…