Table of Contents
Reviews
Building in vitro models of the brain to understand the role of APOE in Alzheimer’s diseaseHuman induced pluripotent stem cell (hiPSC)–based models of the brain will be key to unraveling the role of APOE ɛ4 in the interconnected cellular changes underlying Alzheimer’s disease.
Research Articles
Loss of Amphiregulin drives inflammation and endothelial apoptosis in pulmonary hypertensionThe key pathogenic features of pulmonary hypertension are endothelial apoptosis and vascular inflammation, which are caused by the down-regulation of Amphiregulin, accompanied by HIF-1a and BAD-mediated up-regulation of the target genes such as RRP1B, PHB2, and NCOA6.
Activity-based probe profiling of RNF12 E3 ubiquitin ligase function in Tonne-Kalscheuer syndromeThe authors use photocrosslinking activity-based probes to monitor RNF12/RLIM E3 ubiquitin ligase activity and report the impact of Tonne-Kalscheuer syndrome (TOKAS) patient variants on catalysis.
Multi-omics profiling identifies a deregulated FUS-MAP1B axis in ALS/FTD–associated UBQLN2 mutantsAnalysis 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.
Heparan sulfate proteoglycans mediate prion-like α-synuclein toxicity in Parkinson’s in vivo modelsThis 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.
Proteins implicated in muscular dystrophy and cancer are functional constituents of the centrosomeThis 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.
CryoEM of endogenous mammalian V-ATPase interacting with the TLDc protein mEAK-7The 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.
Identification and characterization of a membrane receptor that binds to human STC1A study using TriCEPS-based ligand–receptor methodology and surface plasmon resonance assays identified that human stanniocalcin-1 binds to insulin-like growth factor-2 receptors in human leukemia monocytic cells with high affinity.
KIF24 depletion induces clustering of supernumerary centrosomes in PDAC cellsDepletion of the centrosomal kinesin KIF24, known to restrain the assembly of primary cilia, suppresses multipolar spindle formation by clustering centrosomes in centrosome-amplified PDAC cells.
STAT3 in tumor fibroblasts promotes an immunosuppressive microenvironment in pancreatic cancerUsing 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.
PVT1 is a stress-responsive lncRNA that drives ovarian cancer metastasis and chemoresistancePVT1 is a YAP1 dependent stress responsive lncRNA that promotes ovarian cancer metastasis and chemoresistance, making PVT1 a promising therapeutic target.
Lack of bombesin receptor–activated protein attenuates bleomycin-induced pulmonary fibrosis in miceEnhanced autophagic activity in fibroblasts due to lack of BRAP homologous protein might contribute to the resistance to pulmonary fibrosis in mice.
The MLL3/4 complexes and MiDAC co-regulate H4K20ac to control a specific gene expression programThe MLL3/4 histone methyltransferase complexes and the histone deacetylase complex MiDAC regulate the histone mark H4K20ac to calibrate gene expression of a common set of target genes.
ScRNA-seq expression of IFI27 and APOC2 identifies four alveolar macrophage superclusters in healthy BALFThere 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.
ERK2 MAP kinase regulates SUFU binding by multisite phosphorylation of GLI1As 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.
Decreasing pdzd8-mediated mito–ER contacts improves organismal fitness and mitigates Aβ42 toxicityThe 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.
Comparative functional genomics identifies unique molecular features of EPSCsThe authors provide a comprehensive resource on proteomics, transcriptomic, and epigenetic level details of EPSCs to shed light on possible molecular pathways regulating their expanded pluripotency potential.
Cdh5-lineage–independent origin of dermal lymphatics shown by temporally restricted lineage tracingTemporally restricted lineage tracing reveals a non-venous source of dermal lymphatic vessels and highlights Cre induction strategy as a critical parameter for stage-specific cell labeling.
Molecular insights into high-altitude adaption and acclimatisation of Aporrectodea caliginosaA megabase genome assembly for Aporrectodea caliginosa is presented with transcriptomic and SNP-based evidence for acclimatisation and adaption to extreme weather conditions found at high altitude.
FKBP4 regulates 5-fluorouracil sensitivity in colon cancer by controlling mitochondrial respirationFKBP4 controls mitochondrial respiration via modulating COA6-mediated biogenesis and activity of mitochondrial complex IV, thereby regulating 5-fluorouracil sensitivity in colon cancer.
Magel2 knockdown in hypothalamic POMC neurons innervating the medial amygdala reduces susceptibility to diet-induced obesityMagel2 knockdown in ARCPOMC neurons innervating the MeA reduces body weight in mice fed with HFD. This effect is associated with increased locomotor activity that is abolished by central GPER blockade.
Semaphorin 6D–expressing mesenchymal cells regulate IL-10 production by ILC2s in the lungGroup 2 innate lymphoid cells (ILC2s) have features specific to the niches in which they reside, and we found that semaphorin 6D signaling in the lung niche controls IL-10 production by ILC2s.
The human RNA polymerase I structure reveals an HMG-like docking domain specific to metazoansWe characterize the human RNA polymerase I by evolutionary biochemistry and cryo-EM revealing a built-in structural domain that apparently serves as transcription factor–binding platform in metazoans.
Dose-dependent phosphorylation and activation of Hh pathway transcription factorsThe Hh gradient is translated into a phosphorylation gradient of Ci/Gli at multiple Fu/CK1 phosphorylation sites, which progressively increases CiA/GliA activity by gradually alleviating Sufu-mediated inhibition.
Mitochondrial stress-induced GFRAL signaling controls diurnal food intake and anxiety-like behaviorMuscle mitochondrial stress signals to the brain via hindbrain-specific GFRAL receptor signaling to promote hypothalamic CRH induction, which associates with GFRAL-dependent modulation of systemic energy metabolism, diurnal food intake, and anxiety-like behavior.
Mechanistic and pharmacodynamic studies of DuoBody-CD3x5T4 in preclinical tumor modelsThis study provides in-depth insight into the mechanism of action and in vivo pharmacodynamic markers of a CD3x5T4 bispecific antibody in preclinical in vitro and in vivo solid cancer models.
α-Actinin-4 recruits Shp2 into focal adhesions to potentiate ROCK2 activation in podocytesα-Actinin-4 is crucial in the regulation of Shp2 FA targeting to enhance ROCK2-mediated actomyosin contractility and thereby strengthening cell adhesion and cytoskeletal architecture in podocytes.
Sibling rivalry among the ZBTB transcription factor family: homodimers versus heterodimersBTB domains potentially can form homo- or heterodimers. The study examines the dimerization choice of several BTB domains and finds only one heterodimer, while all tested pairs can homodimerize.
Gain-of-function genetic screens in human cells identify SLC transporters overcoming environmental nutrient restrictionsThe authors present a CRISPRa-based gain-of-function approach to systematically uncover solute carriers sustaining cellular fitness upon limiting amino acid concentrations.
Translatome profiling in fatal familial insomnia implicates TOR signaling in somatostatin neuronsBauer and colleagues report that among the six neuron types studied, somatostatin neurons have an unexpectedly strong and similar response to two distinct genetic prion diseases before disease onset.
Corrections
- Correction: The intracellular pathogen Francisella escapes from adaptive immunity by metabolic adaptation
This study shows that this metabolic adaptation allows the intracellular bacterial pathogen Francisella tularensis to escape recognition by the host adaptive immunity.
Correction: CDKL3 promotes osteosarcoma progression by activating Akt/PKBThis study demonstrates that CDKL3 regulates Akt activation and its downstream targets to promote OS progression, creating a therapeutically targetable vulnerability in treatment of OS.
