Base by Base

Nihata A et al., PNAS - This PNAS study describes the development of EKV, a humanized dividing cell line that propagates bona fide sporadic CJD (sCJD) prions, and the Human Prion Assay (HPA), a cell-based method that quantifies infectivity with sensitivity comparable to transgenic mouse bioassay while enabling rapid therapeutic screening. Key terms: sCJD, EKV cells, Human Prion Assay, prion infect...

Abson KL et al., PNAS - A cross-species synthesis and theory paper showing that simple molecular diversity metrics poorly predict short-term adaptive potential. The authors compiled >2,100 quantitative genetics estimates (evolvability and heritability) across ~193 eukaryotic species and compared them to nucleotide diversity (π) and microsatellite heterozygosity (He). They find nucleotide divers...

Shin J et al., PNAS - This episode examines a large transcriptome compendium (PRECISE-NP881) that profiles E. coli K-12 MG1655 across 43 carbon substrates. Independent component analysis resolved 137 iModulons, including 25 carbon-catabolism modules that organize substrates into four activity-defined groups tied to growth rate, substrate chemistry, metabolic entry routes, and proteome allocation....

Tsakiria E et al., Proceedings of the National Academy of Sciences (PNAS) - Using Tau knockout mice and the C. elegans PTL-1 deletion, this study shows that loss of wild-type Tau promotes a conserved shift toward mitochondrial fusion, increases respiratory activity, membrane potential and mitophagy, raises ROS, and enhances stress resilience. The adaptive phenotypes depend on mitofusin/FZO-1 and a...

Norberg ES et al., Proceedings of the National Academy of Sciences - Using metal‑responsive fluorescent Salmonella reporters, calf intestinal loops, and CRISPR edited epithelial cells, this study shows that the divalent metal transporter SLC11A2 is recruited to Salmonella‑containing vacuoles and restricts Fe2+ and Mn2+, limiting intracellular bacterial replication. Key terms: SLC11A2, nutritional...

Synowiec A et al., Proceedings of the National Academy of Sciences (PNAS) - This episode examines a PNAS study using fetal, pediatric, and adult human intestinal enteroids to show that physiological temperature and developmental stage jointly determine susceptibility to HCoV-229E, with implications for extrapulmonary coronavirus infection and therapeutic testing. Key terms: HCoV-229E, intestinal e...

Úbeda F et al., Proceedings of the National Academy of Sciences (PNAS) - A population-genetic model explains why sequence-specific PRDM9-guided recombination hotspots can evolve and persist alongside non-PRDM9 hotspots by trading off reduced overall binding for increased symmetric binding that more often yields crossovers. Key terms: PRDM9, recombination hotspots, biased gene conversion, symmetric...

Bošković F et al., Proceedings of the National Academy of Sciences - This study introduces RUNA, a reversible chemistry that selectively labels uridine/thymidine to map nucleic acids across membranes, and uses it to show that most exosomal DNA is surface-exposed, increases after PARP inhibitor treatment, and alters macrophage uptake and activation. Key terms: RUNA, exosomes, surface DNA, macrophag...

Schnaiter et al et al., The American Journal of Human Genetics - Schnaiter et al. pooled Myriad MyChoice HRD+ CDx results from four cohorts (4,943 HGOC tumors) to test whether tumor HRD-related genomic instability scores (HRD-GIS) provide evidence for BRCA1 and BRCA2 variant classification under ACMG/AMP criteria. Key terms: homologous recombination deficiency, genomic instability score (HRD-GIS),...

Baya N et al., The American Journal of Human Genetics 113, 1–19 (2026) - Baya et al. applied a misalignment framework to UK Biobank polygenic scores and exomes and found that individuals whose observed phenotypes deviate from polygenic expectation are enriched for rare damaging variants across multiple traits and diseases. Key terms: polygenic scores, rare variants, misalignment, liability thresho...

Fluri R et al., The American Journal of Human Genetics - This episode examines a cohort study of 16 individuals with de novo LDB1 variants that reveals two overlapping but distinct neurodevelopmental phenotypes tied to variant location. Functional assays and Drosophila models demonstrate loss-of-function effects for N-terminal variants and dominant-negative effects for C-terminal variants. Key ter...

Mastrorosa F et al., The American Journal of Human Genetics - Long-read assemblies and epigenetic mapping of chromosome 21 centromeres in families with trisomy 21 reveal centromere size diversity, two cases of extreme maternal centromere size asymmetry, and no global enrichment of small centromeres in affected individuals. Key terms: trisomy 21, centromere, alpha-satellite, long-read sequencing, m...

Shi Z et al., The American Journal of Human Genetics - A large GWAS meta-analysis across five biobanks (8,969 cases, 1,962,542 controls) identifies five genome-wide significant loci for Ménière disease, implicating developmental regulators EYA1/EYA4 and retinoic acid metabolism genes including CYP26A1. Integrative fine-mapping, eQTL, and single-cell expression place these signals in inner ear cell...

Snyder J et al., Proceedings of the National Academy of Sciences (PNAS) - Longitudinal VAF measurements from 67 JAK2V617F-positive participants in the Danish GESUS study were analyzed with a Moran-process stem cell model and ABC-SMC to infer per-individual self-renewal advantages and assess prognostic value for MPN progression. Key terms: JAK2V617F, clonal hematopoiesis, Moran model, myeloprolifer...

Seidel et al., Nature Communications - SciPhy is a BEAST2-integrated Bayesian framework that models sequential CRISPR‑based insertion edits to jointly infer time-scaled single-cell lineage trees, editing dynamics, and population growth. The authors validate SciPhy on simulations and apply it to HEK293T monoclonal expansion and murine gastruloid datasets, showing improved tree and branch-length inf...

Stannard A et al., Proceedings of the National Academy of Sciences (PNAS) - This episode summarizes a PNAS study that uses a FRET-responsive DNA tweezers nanosensor to detect and quantify sequence-dependent interactions between intact double-stranded DNA duplexes in ionic solutions. Key terms: homologous recognition, double-stranded DNA, electrostatic interactions, DNA nanosensor, divalent cations...

Green R et al., PNAS - Collating >100,000 base-pair substitutions from 32 mutation-accumulation experiments, this study shows that sequence context well beyond adjacent bases — up to ±6 bp and even hundreds of bp — shapes mutational biases in E. coli and interacts with DNA repair. Key terms: mutational bias, sequence context, Escherichia coli, mismatch repair, mononucleotide runs. Study Highlig...

Gaudio HA et al., Nature Communications - This episode examines a systematic benchmark of six commercial large language models applied to plasma cell-free RNA across three clinical cohorts, assessing LLM-driven gene-panel nomination and autonomous classifier construction versus conventional statistical workflows. Key terms: large language models, cell-free RNA, biomarker discovery, machine learnin...

Vambe D et al., Nature Communications - This study reports the programmatic introduction of targeted next-generation sequencing (tNGS) in Eswatini and shows that tNGS detected large amounts of rifampicin and bedaquiline resistance missed by routine diagnostics. Among 234 patient samples, tNGS reclassified many infections, revealed frequent co-occurrence of rpoB I491F and Rv0678 mutations, and guid...

Lara MK et al et al., Nature Communications - Large GWAS in 836 outbred HS rats identifies six loci linked to cocaine self-administration traits, highlighting Ces1 carboxylesterase genes and other loci overlapping human substance-use genetics. Key terms: cocaine use disorder, GWAS, Heterogeneous Stock rats, Ces1, addiction-like behavior. Study Highlights: The study performed a genome-wide associat...

Dr. Sandra Kaufmann, The Kaufmann Anti-Aging Institute - Dr. Sandra Kaufmann — physician, scientist and athlete — set out to understand aging and fight it with science. This episode is a guided overview of her book, featured with the author's permission: why our cells age (mitochondria, genetic information systems, quality control and maintenance, immunity, and waste management) and the families o...

Gätgens C et al., PNAS - This episode examines how DNA-intercalating molecules like daunorubicin block bacteriophage infection at an early stage, causing an abortive-infection-like outcome via toxic phage products and showing synergy with nucleic-acid targeting defenses. Key terms: daunorubicin, abortive infection, bacterial immunity, phage-host interactions, DNA intercalators. Study Highlights: U...

PNAS - This study identifies crotonylation as a posttranslational modification of c-Myc that reduces its transcriptional and oncogenic activity. Key lysines K289 and K298 are crotonylated; loss of crotonylation (including a cancer-derived K298N mutant) enhances Skp2 binding and tumorigenesis. Key terms: c-Myc, crotonylation, Skp2, posttranslational modification, oncogenesis. Study Highlights: The...

Huang X et al., Proceedings of the National Academy of Sciences (PNAS) - This episode summarizes a PNAS study reporting CD163‑targeted lipid nanoparticles that deliver FAP‑specific CAR mRNA to liver macrophages in situ, producing CAR‑macrophages that clear activated hepatic stellate cells and promote fibrosis resolution in mouse models. Key terms: FAP‑CAR, macrophage, lipid nanoparticles, liver fi...

Andrade J et al., PNAS - Analysis of three long-term cohorts in the Philippines and Thailand shows antibody titers wane over years and that homotypic dengue reinfections are common and required to explain population-level age–titer patterns. Key terms: dengue, homotypic reinfection, antibody kinetics, cohort study, mathematical modelling. Study Highlights: The authors analyzed serology and PCR sur...