Best basebybase.podcast@gmail.com (Gustavo Barra Podcasts (2025)

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

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17h ago18:27

18:27

️ 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

1d 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

3d 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

4d ago20:29

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️ 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

5d 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

6d 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

7d 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

7d 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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208: ZAK, Collided Ribosomes, and the Stress Switch 15:55

9d 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

9d 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

11d 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

12d 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

13d 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

13d 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

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

16d 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

17d 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

18d 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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198: Mechanical Confinement and the Shape-Shifting Life of Melanoma Cells 15:47

19d 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

19d 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

21d 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

22d 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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194: Bayesian History of Science: Watson and Crick and the Structure of DNA 14:29

23d ago14:29

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️ Episode 194: Bayesian History of Science: Watson and Crick and the Structure of DNA In this episode of PaperCast Base by Base, we explore how Bayesian reasoning can be used to reconstruct the famous discovery of the DNA double helix by James Watson and Francis Crick, following the sequence of structural models proposed in the early 1950s and the …

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193: SARM1, DNA, and the Death Signal 15:00

23d ago15:00

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️Episode 193: SARM1, DNA, and the Death Signal In this episode of PaperCast Base by Base, we explore how the axon-degenerating enzyme SARM1 acts as a double-stranded DNA sensor that triggers NAD+ loss, cell death, and chemotherapy-induced neuropathy, opening up new possibilities for neuroprotective therapies. Study Highlights: The authors show that…

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192: At Base-Pair Resolution: Chromatin’s Cis-Regulatory Conversations 14:24

25d ago14:24

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️Episode 192: At Base-Pair Resolution: Chromatin’s Cis-Regulatory Conversations In this episode of PaperCast Base by Base, we explore how base-pair resolution maps of chromatin contacts reveal a unified, biophysical model of communication between enhancers, promoters, and other cis-regulatory elements in mammalian cells. Study Highlights: Using Mic…

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191: CATphishing: Synthetic Learning as an Alternative to Federated Learning in MRI 19:17

26d ago19:17

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️ Episode 191: CATphishing: Synthetic Learning as an Alternative to Federated Learning in MRI In this episode of PaperCast Base by Base, we explore a Nature Communications study that proposes CATphishing—an approach that uses latent diffusion models to generate site-specific synthetic 3D brain MRIs for collaborative training without sharing raw dat…

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190: Single-Cell Networks Reveal Cell Type–Specific Mechanisms in Type 2 Diabetes 15:43

27d ago15:43

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️ Episode 190: Single-Cell Networks Reveal Cell Type–Specific Mechanisms in Type 2 Diabetes In this episode of PaperCast Base by Base, we explore how a network-based analysis of single-cell RNA sequencing from human pancreatic islets uncovers cell type–specific gene-regulatory changes that help explain type 2 diabetes pathophysiology. Study Highlig…

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189: DNA methylation patterns facilitate tracing the origin of neuroendocrine neoplasms 14:22

28d ago14:22

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️ Episode 189: DNA methylation patterns facilitate tracing the origin of neuroendocrine neoplasms In this episode of PaperCast Base by Base, we explore how genome-wide DNA methylation profiling can pinpoint the organ of origin for neuroendocrine neoplasms (NEN), with a special focus on lesions detected in the liver and long-debated “primary hepatic…

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188: Proteomics + Machine Learning for Lyme Neuroborreliosis Diagnosis 16:51

29d ago16:51

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️ Episode 188: Proteomics + Machine Learning for Lyme Neuroborreliosis Diagnosis In this episode of PaperCast Base by Base, we explore how large‑scale mass‑spectrometry proteomics of cerebrospinal fluid and plasma, paired with supervised machine learning, can distinguish Lyme neuroborreliosis from viral meningitis and non‑LNB controls in adults. St…

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187: Gapped PARP + Tumor‑Targeted TOP1 in Advanced Tumors 16:13

30d ago16:13

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️ Episode 187: Gapped PARP + Tumor‑Targeted TOP1 in Advanced Tumors In this episode of PaperCast Base by Base, we explore a phase I dose‑escalation trial that pairs a tumor‑targeted topoisomerase I inhibitor (CRLX101, a nanoparticle camptothecin) with optimized, gapped scheduling of the PARP inhibitor olaparib to reduce toxicity while preserving ef…

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186: TNFα–TGFβ Axis Disrupts Nasal Epithelium in Post‑COVID Syndrome 15:22

1M ago15:22

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️ Episode 186: TNFα–TGFβ Axis Disrupts Nasal Epithelium in Post‑COVID Syndrome In this episode of PaperCast Base by Base, we explore a single‑cell RNA‑seq study of nasal biopsies showing that persistent immune signaling—not residual virus—drives aberrant epithelial differentiation in people with post‑COVID syndrome. fileciteturn1file0 Study High…

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185: Altered Milk Tryptophan in Women Living with HIV 14:59

1M ago14:59

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️ Episode 185: Altered Milk Tryptophan in Women Living with HIV In this episode of PaperCast Base by Base, we explore a longitudinal metabolomics study of human milk that reveals how maternal HIV infection reshapes tryptophan metabolism across lactation, with potential implications for infant immunity, growth, and neurodevelopment. Study Highlights…

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184: High-Accuracy Multiethnic XGBoost for Skin Cancer Identification 17:44

1M ago17:44

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️ Episode 184: High-Accuracy Multiethnic XGBoost for Skin Cancer Identification In this episode of PaperCast Base by Base, we explore a large-scale study that builds a risk factor–based XGBoost model using the All of Us cohort to accurately identify patients with skin cancer across diverse ancestries. Study Highlights: Analyzing more than 400,000 p…

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183: The Genetic Lottery Goes to School: Better Schools Compensate for Genetic Differences 18:05

1M ago18:05

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️ Episode 183: The Genetic Lottery Goes to School: Better Schools Compensate for Genetic Differences In this episode of PaperCast Base by Base, we explore a large causal study from Norway asking whether school quality can offset genetic differences in students’ academic skills. Using parent–offspring genetic trios from the Norwegian Mother, Father,…

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182: Genotypic, Functional, and Phenotypic Characterization in CTNNB1 Neurodevelopmental Syndrome 16:18

1M ago16:18

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️ Episode 182: Genotypic, Functional, and Phenotypic Characterization in CTNNB1 Neurodevelopmental Syndrome In this episode of PaperCast Base by Base, we explore a large cross-sectional cohort study that integrates genetics, cellular functional assays, and deep phenotyping to map the landscape of CTNNB1 neurodevelopmental syndrome. The authors anal…

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181: Creatine Transporter SLC6A8: Conservation and Variant Impact 12:44

1M ago12:44

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️ Episode 181: Creatine Transporter SLC6A8: Conservation and Variant Impact In this episode of PaperCast Base by Base, we explore how the creatine transporter gene SLC6A8 (CRT1) is evolutionarily conserved across terrestrial mammals and how disease-associated variants alter creatine uptake in vitro, shedding light on genotype–phenotype relationship…

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180: Leveraging Global Genetics Resources for Equitable Polygenic Prediction 22:11

1M ago22:11

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️ Episode 180: Leveraging Global Genetics Resources for Equitable Polygenic Prediction In this episode of PaperCast Base by Base, we explore how multi-ancestry genome-wide association study resources and modern polygenic score methodologies can improve prediction accuracy across African, East Asian, and European populations, with a focus on practic…

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179: Mosaicism for Autosomal Trisomies: Maternal Age, UPD, and Reproductive History in 1,266 Cases 16:49

1M ago16:49

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️ Episode 179: Mosaicism for Autosomal Trisomies: Maternal Age, UPD, and Reproductive History in 1,266 Cases In this episode of PaperCast Base by Base, we explore a comprehensive literature analysis of 1,266 reported cases of autosomal trisomy mosaicism, contrasting prenatal cohorts—true fetal mosaicism and confined placental mosaicism—with postnat…

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178: TP53 Reduced Penetrance: Predictive Features and Clinical Implications 15:59

1M ago15:59

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️ Episode 178: TP53 Reduced Penetrance: Predictive Features and Clinical Implications In this episode of PaperCast Base by Base, we explore how a large ClinVar-anchored analysis integrates functional assays, computational predictors, immunogenicity estimates, allele frequencies, and clinical presentation to identify TP53 variants with reduced penet…

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177: Biallelic MCM8/MCM9 Variants: From Hypogonadism to Cancer Predisposition 17:04

1M ago17:04

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️ Episode 177: Biallelic MCM8/MCM9 Variants: From Hypogonadism to Cancer Predisposition In this episode of PaperCast Base by Base, we explore a multi‑cohort clinical–genomic study that delineates the phenotype of individuals with biallelic germline variants in MCM8 or MCM9, clarifying links to polyposis and early‑onset cancers in addition to the lo…

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176: FAHD1 and the Pyruvate-Driven Evolution of Hepatocellular Carcinoma 19:32

1M ago19:32

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️ Episode 176: FAHD1 and the Pyruvate-Driven Evolution of Hepatocellular Carcinoma In this episode of PaperCast Base by Base, we explore how multi-omics integration—spanning single-cell transcriptomics, spatial mapping, and causal genetic inference—uncovers a pyruvate-hyperactive epithelial subpopulation in hepatocellular carcinoma and identifies F…

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175: Predictive Prioritization of Pancreatic Enhancers Linked to Disease Risk 19:13

1M ago19:13

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️ Episode 175: Predictive Prioritization of Pancreatic Enhancers Linked to Disease Risk In this episode of PaperCast Base by Base, we explore how enhancer–promoter 3D chromatin maps from five primary human pancreatic cell types were transformed into graph “tree” models to quantify enhancer connectivity and prioritize elements most critical for cell…

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174: TMEM217–SLC9C1: Wiring the cAMP Switch for Sperm Motility and Male Fertility 16:40

1M ago16:40

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️ Episode 174: TMEM217–SLC9C1: Wiring the cAMP Switch for Sperm Motility and Male Fertility In this episode of PaperCast Base by Base, we explore a PNAS study revealing how TMEM217 forms a complex with the sperm-specific Na+/H+ exchanger SLC9C1 to organize cAMP signaling, sustain motility, and enable fertilization in mice. Study Highlights: Using p…

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173: Bottlebrush Block Copolymer Shields Muscles and Prevents DMD Onset 20:12

1M ago20:12

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️ Episode 173: Bottlebrush Block Copolymer Shields Muscles and Prevents DMD Onset In this episode of PaperCast Base by Base, we explore a PNAS study showing how a synthetic bottlebrush block copolymer can act as a powerful membrane stabilizer to protect dystrophin-deficient muscle in Duchenne muscular dystrophy. Study Highlights: Researchers engine…

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172: When Random DNA Fights Back: De Novo Gene Birth as Antiphage Defense 19:44

1M ago19:44

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️ Episode 172: When Random DNA Fights Back: De Novo Gene Birth as Antiphage Defense In this episode of PaperCast Base by Base, we explore a PNAS study showing that short, previously nongenic DNA sequences can quickly evolve into genes that help bacteria survive phage attack, illuminating early steps of gene birth and the host–virus arms race. file…

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171: Virulence Hierarchies in the Tuberculosis Complex—What Makes Some Lineages Deadlier? 16:14

2M ago16:14

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️ Episode 171: Virulence Hierarchies in the Tuberculosis Complex—What Makes Some Lineages Deadlier? In this episode of PaperCast Base by Base, we explore a new PNAS study that directly compares the virulence of Mycobacterium tuberculosis, M. bovis, and M. orygis across natural and laboratory hosts to uncover why animal-adapted lineages can be so de…

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170: Maternal Age, Meiotic Recombination Failure, and Triploidy in Humans 17:03

2M ago17:03

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️ Episode 170: Maternal Age, Meiotic Recombination Failure, and Triploidy in Humans In this episode of PaperCast Base by Base, we explore how maternal age and failures of meiotic recombination shape the origins of triploid conceptions in humans, drawing on large-scale preimplantation genetic testing datasets from ICSI-derived embryos. Study Highlig…

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169: Deep mutational scanning of the insulin receptor guides precision therapy for insulin resistance 21:13

2M ago21:13

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️ Episode 169: Deep mutational scanning of the insulin receptor guides precision therapy for insulin resistance In this episode of PaperCast Base by Base, we explore how a comprehensive deep mutational scan of the human insulin receptor ectodomain maps the effects of ~14,000 missense variants on surface expression, insulin binding, and downstream s…

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168: Low circulating miR-190a-5p predicts progression of chronic kidney disease 19:10

2M ago19:10

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️ Episode 168: Low circulating miR-190a-5p predicts progression of chronic kidney disease In this episode of PaperCast Base by Base, we explore how unbiased small RNA sequencing and multi-cohort validation identify circulating miR-190a-5p as a prognostic marker of chronic kidney disease that reflects tubular health and points to a potential therape…

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167: DeepScence: Detecting Senescent Cells at Single-Cell and Spatial Resolution 21:40

2M ago21:40

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️ Episode 167: DeepScence: Detecting Senescent Cells at Single-Cell and Spatial Resolution In this episode of PaperCast Base by Base, we explore a Cell Genomics study introducing DeepScence, a deep-learning autoencoder that leverages a compact “CoreScence” gene set to identify senescent cells across single-cell and spatial transcriptomics data, out…

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