Gustavo Barra

Base by Base

Science EN ↓ 413 episodes

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.

Author

Gustavo Barra

Category

Science

Podcast website

basebybase.com

Latest episode

Jul 9, 2026

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Episodes

263: Bifacial γPNA triplets target rCUG repeats and displace MBNL1 in Myotonic Dystrophy type 1 18.01.2026

Perera J et al., Proc. Natl. Acad. Sci. U.S.A. 2026.123:e2507065123 - Gamma-PNA triplet ligands with Janus bases selectively bind expanded rCUG repeats, displace MBNL1, and show length-dependent cooperativity with partial splicing rescue. Key terms: rCUG repeats, gamma PNA, Janus bases, MBNL1 displacement, myotonic dystrophy type 1. Study Highlights: The authors designed compact three-unit bifacia...

262: Human Langerhans cells reprogrammed by tick saliva (CXCR4/CCR7 migration and IDO1/IRF4 tolerance) 17.01.2026

Strobl et al., Nature Communications - Human epidermal Langerhans cells exposed to Ixodes ricinus tick saliva and Borrelia burgdorferi adopt a tolerogenic state with CXCR4/CCR7-driven emigration that impairs T cell priming. Key terms: Langerhans cells, tick saliva, Borrelia burgdorferi, CXCR4/CCR7 migration, immune tolerance. Study Highlights: The study uses clinical human tick bite biopsies, an e...

261: MHz-XPCS reveals anomalous ferritin diffusion and nanoscale cage trapping 16.01.2026

Girelli et al., Nature Communications - 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. Key terms: ferritin, MHz-XPCS, anomalous diffusion, cage effects, hydrodynamic function. Study Highlights: The study probes crowded ferritin solutions using megahertz X-ray Photon Correlation Sp...

260: TSS hypermutability in human germline linked to RNAP II stalling, R-loops and early embryonic mosaics 15.01.2026

Nature Communications - Transcription start sites experience a high influx of heritable variants fueled by early development Music: Enjoy the music based on this article at the end of the episode. Article title: Transcription start sites experience a high influx of heritable variants fueled by early development Journal: Nature Communications DOI: 10.1038/s41467-025-66201-0 License: CC BY 4.0 Inter...

259: Ku filaments that hold DNA together 14.01.2026

Zahid S et al., Nature Communications, doi:10.1038/s41467-025-65609-y - 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. Key terms: Ku-Mtb, non-homologous end joining, cryo-EM, DNA synapsis, Mycobacterium tuberculosis. Study Highlights: Deletion of ku...

258: Correcting GC bias in metagenomes 13.01.2026

Holcik L et al., Nature Communications, doi:10.1038/s41467-025-65530-4 - 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 Kraken2/...

257: PSMC5: proteasomes, immunity and neurodevelopment 12.01.2026

Küry S et al., Nature Communications, doi:10.1038/s41467-025-65556-8 - 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, mit...

256: Compartmental control of VSG silencing 11.01.2026

Antunes et al., Nature Communications - 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 chromosomes are organized into...

255: Lipids, Ions and the AE1 Elevator 10.01.2026

Chen T et al., Nature Communications - 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...

254: Rescuing the replisome at a nick 09.01.2026

Winterhalter et al., Nature Communications - 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, SSB. Study Highlights: Site-specif...

253: Nap1 and histone acetylation tune chromatin condensates 08.01.2026

Gao J et al., Nature Communications - 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 d...

252: Keratinocytes to cSCC: genetic steps 07.01.2026

Deivendran D et al., Nature Communications, doi:10.1038/s41467-025-65687-y - 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. Key terms: keratinocytes, actinic keratosis, TP53, ARID2, spatial transcriptomics. Study Highlights: Single-cell genotyping of 137 ker...

251: MuSCs, laminin-α2 and LAMA2 MD 06.01.2026

McGowan TJ et al., Nature Communications, doi:10.1038/s41467-025-65703-1 - 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. Key terms: laminin-α2, muscle stem cells, LAMA2 MD, regeneration, proliferation. Study Highlights: Activat...

250: CIP2A–TOPBP1: Mitotic repair via MiDAS and MMEJ 05.01.2026

Nieminuszczy J et al., Nature Communications, doi:10.1038/s41467-025-65594-2 - 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. Key terms: CIP2A, TOPBP1, SLX4, MiDAS, MMEJ. Study Highlights: TOPBP1 BRCT1/2 binds SLX4 phosphorylated at Thr1260, a CDK1-dependent modi...

249: PCM1 links centrosome asymmetry to endosome dynamics 04.01.2026

Zhao X et al., Nature Communications - 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. Key terms: PCM1, centrosome asymmetry, endosome dynamics, radial glia progenitors, Notch signaling. Study...

248: Disruption of PIKfyve triggers lysosomal repair and mitochondrial adaptation 03.01.2026

Kutchukian C et al., Nature Communications - 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. Key terms: PIKfyve, PI4KIIα, PI(4)P, ULK1, lysosomal repair. Study Highlights: PIKfyve complex disruption or pharmacolog...

247: Genome graphs reveal structural variation in M. tuberculosis 02.01.2026

Canalda-Baltrons A et al., Nature Communications - Long-read assemblies and a pangenome reference graph uncover widespread structural variants that shape Mycobacterium tuberculosis evolution and contribute to drug resistance. Key terms: structural variation, pangenome graph, Mycobacterium tuberculosis, drug resistance, long-read sequencing. Study Highlights: The authors built an M. tuberculosis pa...

246: SV2A structural pharmacology and allosteric occlusion 01.01.2026

Pidathala S et al., Nature Communications - High-resolution cryo-EM structures of human SV2A reveal that orthosteric ligands induce an occluded MFS conformation and a secondary allosteric pocket modulates ligand binding. Key terms: SV2A, allosteric modulation, cryo-EM, levetiracetam, padsevonil. Study Highlights: The authors report sub-3 Å cryo-EM structures of human SV2A in the apo state and in c...

245: Benchmarking DNA foundation models 31.12.2025

Feng H et al., Nat Commun - A comprehensive, unbiased benchmark compares five DNA foundation models across 57 datasets and multiple tasks, finding mean token embeddings improve classification and that model strengths vary by task and pre-training. Key terms: DNA foundation models, mean token embedding, sequence classification, variant effect, gene expression. Study Highlights: The study evaluated...

244: NEK7 couples SDHB to preserve mitochondrial electron transport and limit liver fibrosis 30.12.2025

Sun Z et al., Nature Communications - Mitochondrial NEK7 is imported via MTS peptides, binds SDHB to stabilize complex II conformation, prevent reverse electron transport and ROS, and thereby protects against spontaneous and experimentally induced liver fibrosis. Key terms: NEK7, SDHB, reverse electron transport, ROS, liver fibrosis. Study Highlights: NEK7 localizes to hepatocyte mitochondria thro...

243: Genome-wide UVB GxE study finds 162 vitamin D variants 29.12.2025

Shraim R et al., Nat Commun - A GWIS of 338,977 UK Biobank White British participants using a cumulative weighted ambient UVB measure identified 307 independent loci for 25-hydroxyvitamin D, including 162 novel variants. Key terms: vitamin D, gene-environment interaction, ambient UVB, GWAS, circadian rhythm. Study Highlights: The study linked a cumulative and weighted ambient UVB (CW-D-UVB) dose f...

242: AAV9-fcMISv2 gene therapy prevents pregnancy in female cats 28.12.2025

Godin P et al., Nature Communications - A single intramuscular injection of an AAV9 vector encoding feline anti‑Müllerian hormone (fcMISv2) in prepubertal kittens produced sustained supraphysiological AMH, was well tolerated, and prevented breeding‑induced ovulation and pregnancy in adult females. Key terms: gene therapy, anti-Müllerian hormone, feline sterilization, adeno-associated virus, popula...

241: Wagyu T2T reveals a cattle X neocentromere 27.12.2025

Pineda PS et al., Nature Communications - A telomere-to-telomere Wagyu assembly uncovers a natural neocentromere on the cattle X formed by inverted repeats and transposable element expansion, adds hundreds of new genes, and improves variant discovery. Key terms: cattle genomics, neocentromere, centromere evolution, telomere-to-telomere, structural variants. Study Highlights: The UOA_Wagyu_1 haplot...

240: CYFIP1 controls cortical axon development by modulating calcium 26.12.2025

Ricci C et al., Nature Communications - Reduction of CYFIP1 delays callosal axon growth and arborization by lowering intracellular calcium and impairing mitochondrial function. Key terms: cyfip1, axon development, calcium, mitochondria, callosal connectivity. Study Highlights: In vivo, Cyfip1+/- mice show delayed callosal axon growth at P5 and reduced axonal branching during P15 arborization that...

239: Genomic Adaptations of the Svalbard Reindeer 25.12.2025

Genome Biology and Evolution - The Genomic Basis of the Svalbard Reindeer’s Adaptation to an Extreme Arctic Environment Music: Enjoy the music based on this article at the end of the episode. Article title: The Genomic Basis of the Svalbard Reindeer’s Adaptation to an Extreme Arctic Environment Journal: Genome Biology and Evolution DOI: 10.1093/gbe/evaf160 License: This episode is based on an open...

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