Base by Base

454: Efavirenz retarda a doença priônica mexendo no colesterol do cérebro [PT]

Ali T et al., JCI Insight - Um antirretroviral aprovado para HIV, dado por via oral em microdose, prolongou a sobrevida de camundongos que carregam a proteína priônica hu

453: Efavirenz slows sCJD progression by reshaping brain cholesterol

Ali T et al., JCI Insight - Repurposed low-dose efavirenz slowed disease progression and extended survival in tg650 mice inoculated with MM1 sCJD prions by activating CYP

452: Reduzir a PrP funciona em todas as linhagens [PT]

Minikel EV et al., Nucleic Acids Research - Este estudo testa a redução da proteína priônica (PrP) por oligonucleotídeos antisense (ASOs) em camundongos, variando doses,

451: Prion protein lowering is disease-modifying across stages and strains

Minikel EV et al., Nucleic Acids Research - This study uses antisense oligonucleotides (ASOs) to lower prion protein (PrP) RNA in mice and shows dose-dependent extension

450: ASOs que reduzem PrP prolongam a sobrevida [PT]

Raymond GJ et al., JCI Insight - This episode covers a 2019 study showing that sequence-specific antisense oligonucleotides (ASOs) targeting the prion protein (PrP) mRNA,

449: siRNA divalente para doença priônica [PT]

Gentile JE et al., Nucleic Acids Research - Discovery and preclinical development of divalent siRNA candidates targeting PRNP, identifying 2439-s4 as a potent, durable hu

448: PrP‑lowering ASOs prolong survival in prion‑infected mice

Raymond GJ et al., JCI Insight - This study tests antisense oligonucleotides (ASOs) targeting Prnp in wild‑type mice infected with RML prions and shows that sequence‑spec

447: Divalent siRNA for prion disease

Gentile JE et al., Nucleic Acids Research - This study develops and tests divalent siRNA molecules that lower prion protein (PrP) in the brain, identifies a potent human-

446: Cilia, Synuclein, and Survival: G51D Mice Reveal a Shared Parkinson’s Pathway

Lin Y‑E et al., PNAS - Knock‑in SncaG51D/G51D mice show selective loss of primary cilia in specific striatal interneurons, astrocytes, piriform cortex PV cells and olfact

445: Why Thymine Survived the UV: Photodamage Pathways Explained

Khosh Abady K et al., PNAS - Spectroscopic comparison of thymine and uracil under 265 nm UVC shows thymine is more photoreactive and absorbs more primordial UVC, yet chan

444: Many-eyes or Sentinels? How Cost Curvature Shapes Collective Vigilance

Pilgrim C et al., PNAS - A minimal analytical model shows that whether animal groups adopt distributed low-level vigilance (many-eyes) or concentrated high-vigilance role

443: 5D‑ASO boosts exon 51 skipping and restores dystrophin in DMD models

Feng P et al., PNAS - This paper describes a bipartite antisense oligonucleotide (5D‑ASO) design that appends a short 5′ splice site decoy tail to improve exon skipping,

442: When pumps go missing: Ca2+ control of PMCA2 in Tmc1 deafness mutants

Rolseth AB et al., Proceedings of the National Academy of Sciences (PNAS) - This study links reduced Ca2+ entry through mutant TMC1 mechanotransducer channels to decrease

441: Evolutionary mapping of Cav1.3 functional sites

Tang X et al., PNAS - The authors apply an evolutionary sequence-covariation model to the Cav1.3 (CACNA1D) α1-subunit, map predicted pathogenicity onto structural models,

440: DENV-4: Suppressing DNA Repair and Causing Genome Damage

Lamkina EN et al., PNAS - This episode reviews a PNAS brief report showing that DENV-4 infection induces marked DNA damage in infected cells while broadly suppressing tra

439: Coembedding Sequence and Structure: CLSS Maps the Protein Universe

Longo LM et al., PNAS - This episode summarizes a PNAS study introducing CLSS, a contrastive two-tower protein language model that coembeds domain sequences, structures,

438: Mapping AIRE: a proactive atlas of 9,790 missense variants

Axakova A et al., The American Journal of Human Genetics - Axakova et al. generated a variant effect map for AIRE using an insulin‑promoter GFP reporter in HEK293 cells t

437: Cell villages and Dirichlet modeling map human cell fitness genetics

Hanson C et al., The American Journal of Human Genetics - Hanson et al. combine pooled multi-donor human neural progenitor cell "villages" with Townlet, a hierarchical Di

436: KIAP4 and the ARND family: building the Leishmania adhesion plaque

Owino BO et al., PNAS - Using TurboID proximity proteomics and microscopy, researchers identify KIAP4 as the canonical member of a conserved Adhesion Related NTPase-like

435: E. coli TGT binds two tRNAs — cryo-EM reveals dual engagement

Ember M et al., PNAS - This episode examines a cryo-EM study of Escherichia coli tRNA-guanine transglycosylase (TGT) that solves the enzyme structure and its covalent int