Most read article(s)
- Decreasing pdzd8-mediated mito–ER contacts improves organismal fitness and mitigates Aβ42 toxicity
The authors provide the first description of the impact of reducing pdzd8-mediated mito–ER contacts which prolongs lifespan, reduces age-related locomotor decline, and protects against mitochondrial toxins. pdzd8 loss is also protective against neuronal toxicity from Aβ42.
- ERK2 MAP kinase regulates SUFU binding by multisite phosphorylation of GLI1
As a mechanism of crosstalk, potentially relevant to cancer and developmental signaling, ERK2 MAP kinase phosphorylates the Hedgehog-pathway transcription factor GLI1 on three sites, promoting release of the negative regulator SUFU and the consequent activation of GLI1.
- ScRNA-seq expression of IFI27 and APOC2 identifies four alveolar macrophage superclusters in healthy BALF
There are at least 14 AM subtypes; their frequency, along with other immune cells, is highly conserved across individuals, suggesting a specific niche exists for each leukocyte population.
- Heparan sulfate proteoglycans mediate prion-like α-synuclein toxicity in Parkinson’s in vivo models
This study offers new Caenorhabditis elegans models in which feeding with α-synuclein pre-formed fibrils results in prion-like aggregation of host α-synuclein and dopamine neuron degeneration, and these disease phenotypes are regulated by the heparan sulfate proteoglycan pathway.
- Multi-omics profiling identifies a deregulated FUS-MAP1B axis in ALS/FTD–associated UBQLN2 mutants
Analysis of ALS patient-derived and engineered cells revealed that mutant UBQLN2 increases mRNA and protein of MAP1B which is mediated by dephosphorylation of FUS within its RNA-binding domain.
- STAT3 in tumor fibroblasts promotes an immunosuppressive microenvironment in pancreatic cancer
Using a dual recombinase mouse model of pancreatic cancer, investigators uncover genetic evidence for the role of STAT3 signaling in cancer-associated fibroblasts in promoting tumor progression and an immunosuppressive microenvironment.
- CryoEM of endogenous mammalian V-ATPase interacting with the TLDc protein mEAK-7
The structure of mammalian V-ATPase with mEAK-7 shows how a TLDc domain-containing protein can bind the proton pump to form an activity-sensitive interaction.
- Analyzing efficacy, stability, and safety of AAV-mediated optogenetic hearing restoration in mice
This longitudinal study revealed stable expression of the fast-gating channelrhodopsin f-Chrimson in cochlear neurons of mice over at least 2 yr upon a single postnatal AAV dosing of the cochlea.
- Proteins implicated in muscular dystrophy and cancer are functional constituents of the centrosome
This study demonstrates that the muscular dystrophy-associated proteins dystrophin, utrophin, dysferlin, and calpain-3 localize to the centrosome and that their absence leads to excess centrosomes, compromised nuclear morphology, impaired centrosome orientation, and defective microtubule nucleation.
- Drosophila insulator proteins exhibit in vivo liquid–liquid phase separation properties
Drosophila insulator proteins and the cohesin subunit Rad21 coalesce in vivo to form liquid-droplet condensates, suggesting that liquid–liquid phase separation mediates their function in 3D genome organization.