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Research Articles
Drosophila insulator proteins exhibit in vivo liquid–liquid phase separation propertiesDrosophila 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.
RFWD3 and translesion DNA polymerases contribute to PCNA modification–dependent DNA damage toleranceRFWD3 and the translesion DNA polymerases Polκ and Polη, for illudin S and UV DNA lesions, respectively, contribute to PCNA ubiquitination–dependent DNA damage tolerance in human cells.
Dimerization of kringle 1 domain from hepatocyte growth factor/scatter factor provides a potent MET receptor agonistWe designed and characterized a potent full MET receptor agonist consisting of two recombinantly linked HGF/SF kringle 1 domains and demonstrated its potential in epithelial tissue regeneration.
Chr21 protein–protein interactions: enrichment in proteins involved in intellectual disability, autism, and late-onset Alzheimer’s diseaseA large-scale (82) yeast two-hybrid screen focusing on chromosome 21 proteins and their direct interactors revealed enrichment in proteins linked to synapse plasticity, autism, and Alzheimer’s disease.
Novel DNM1L variants impair mitochondrial dynamics through divergent mechanismsNovel DNM1L variants underlie a spectrum of clinical phenotypes and impair mitochondrial and peroxisomal dynamics via divergent mechanisms, with effects on DRP1 protein stability, GTPase activity, and oligomerisation in vitro.
PFKFB4 interacts with ICMT and activates RAS/AKT signaling-dependent cell migration in melanomaGlycolysis regulator PFKFB4 promotes cell migration in metastatic melanoma and normal melanocytes by a non-conventional glycolysis-independent function involving ICMT, RAS, and AKT signaling.
Insight into the mechanism of DNA synthesis by human terminal deoxynucleotidyltransferaseThe role of metal ions and specific interactions of dNTP with active-site amino acid residues in the mechanisms underlying the recognition of nucleoside triphosphates by human terminal deoxynucleotidyltransferase were revealed by pre–steady-state kinetics and molecular dynamics approaches.
RNA-sequencing of single cholangiocyte-derived organoids reveals high organoid-to organoid variabilityWhereas batch variation between organoid cultures is low, inter-culture heterogeneity can be large, even within one well, which might stem from microenvironmental differences within the culture.
A protective role for Drosophila Filamin in nephrocytes via Yorkie mediated hypertrophyNephrocytes lacking key components of the filtration barrier respond by increasing Drosophila Filamin expression, which accumulates at the cell cortex to elicit a protective role.
Human milk inhibits some enveloped virus infections, including SARS-CoV-2, in an intestinal modelHuman milk blocks some enveloped, but not non-enveloped, virus infections in a primary human fetal intestinal model and the transcriptomic data points towards inhibition of entry mediated by ATP1A1.
Ubiquitome profiling reveals a regulatory pattern of UPL3 with UBP12 on metabolic-leaf senescenceA landscape of UPL3-ubiquitinated proteins by ubiquitome profile indicates UPL3 interacting with UBP12 as a hub of regulator on proteolysis-independent regulation and proteolysis-dependent degradation.
The L-NAME mouse model of preeclampsia and impact to long-term maternal cardiovascular healthThe L-NAME mouse model of preeclampsia mimics key aspects of disease in pregnancy, but does not demonstrate the increased long-term risk of cardiovascular disease seen in individuals following preeclampsia.
The conserved Pelado/ZSWIM8 protein regulates actin dynamics by promoting linear actin filament polymerizationPldo/ZSWIM8 is a conserved protein that promotes linear actin polymerization at the expense of branched actin in several contexts, ranging from Drosophila morphogenesis to human cell migration.
Resolution of the curse of dimensionality in single-cell RNA sequencing data analysisThis work formulates a noise reduction method, RECODE, which resolves the curse of dimensionality in noisy high-dimensional data, including scRNA-seq data, for effective downstream analyses.
Bivalent binding of p14ARF to MDM2 RING and acidic domains inhibits E3 ligase functionThis study shows that MDM2 acidic and zinc finger regions weakly interact with the RING domain and a fragment of p14ARF strengthens this interaction to inhibit MDM2 ubiquitin ligase activity.
Efficacy of SARS-CoV-2 vaccination in patients with monoclonal gammopathies: A cross sectional studyUninfected multiple myeloma patients do not develop adequate immunity after SARS-COV-2 vaccination and will clearly benefit from tailored monitoring of immune responses after booster vaccine doses.
Telescoping bimodal latent Dirichlet allocation to identify expression QTLs across tissuesWe present telescoping bimodal LDA, a method to identify complex associations across high-dimensional count data, and we show TBLDA’s behavior for expression QTL mapping for bulk RNA-seq data from 10 tissues in the GTEx data.
Methionine uptake via the SLC43A2 transporter is essential for regulatory T-cell survivalRegulatory T cells survive after IL-2 withdrawal by taking up and using methionine through the SLC43A2 transporter in a Notch1-dependent manner.
Emetine blocks DNA replication via proteosynthesis inhibition not by targeting Okazaki fragmentsThis study clarifies the long-standing misuse of emetine as a lagging strand synthesis-specific inhibitor. Emetine blocks the synthesis of both DNA strands by the inhibition of protein biosynthesis.
Cross talk between glucose metabolism and immunosuppression in IFN-γ–primed mesenchymal stem cellsThis study reveals a novel relationship between mesenchymal stem cell immunomodulation and metabolism and provides a new strategy to improve their therapeutic efficacy in inflammatory diseases.
Mitochondrial impairment and intracellular reactive oxygen species alter primary cilia morphologyThis work shows how altering energetic status and promoting intracellular/mitochondrial ROS induces cell-dependent ciliary impairments, which is relevant in diseases characterized by these features.
Mesenchymal stem cells derived from patients with premature aging syndromes display hallmarks of physiological agingUsing of genome-wide approaches on models from laminopathies with or without progerin accumulation (HGPS, HGPS-L, APS), this study provides new insights on pathways altered during early stages of mesenchymal stem cells differentiation.
ALS-linked loss of Cyclin-F function affects HSP90Analysis of ALS patient cell lines and cyclin-F overexpression and knockout cells identified HSP90AB1 as novel SCFcyclin-F substrate pointing to a loss-of-function mechanism for ALS CCNF mutations.
Ataxin-2, Twenty-four, and Dicer-2 are components of a noncanonical cytoplasmic polyadenylation complexIdentification of components of a noncanonical cytoplasmic polyadenylation machinery in Drosophila expands the diversity of RNA-binding proteins involved in poly(A) tail length control.
RSC and GRFs confer promoter directionality by restricting divergent noncoding transcriptionWe show that the chromatin remodelling complex RSC and general regulatory factors (GRFs) limit transcription in the noncoding divergent direction, thereby increasing the directionality of promoters.
A critique of the hypothesis that CA repeats are primary targets of neuronal MeCP2Using relevant neuronal datasets and in vitro experiments, we show that MeCP2 function depends on methylated CAC (mCAC) sites regardless of their occurrence in CA repeats or elsewhere in the genome.
miR-329– and miR-495–mediated Prr7 down-regulation is required for homeostatic synaptic depression in rat hippocampal neuronsIn rat hippocampal neurons, miRNA-dependent regulation of the synaptic Prr7 protein is required for the homeostatic synaptic depression of excitatory synapses upstream of the CDK5-SPAR pathway.
Timapiprant, a prostaglandin D2 receptor antagonist, ameliorates pathology in a rat Alzheimer’s modelPGD2 is a major brain prostaglandin and we report that timapiprant that is an antagonist for the PGD2 receptor DP2 reduces pathology and cognitive deficits in a transgenic rat model of Alzheimer’s.
Synthetic evolution of herbicide resistance using a T7 RNAP–based random DNA base editorA chimeric fusion of T7 RNAP and deaminase edits the DNA under the T7 promoter in plant cells. It directs the continuous synthetic evolution of OsALS to produce variants with herbicide resistance.
Nodal and churchill1 position the expression of a notch ligand during Xenopus germ layer segregationChurchill and Nodal signaling, which participate in vertebrates’ germ layer induction, position a domain of Delta/Notch activity, which refines germ layer boundaries during frog gastrulation.
Non-canonical miRNA-RNA base-pairing impedes tumor suppressor activity of miR-16In uveal melanoma tumors, the RNA decay activity of the tumor suppressor miR-16 is impaired by sponge RNAs. These RNAs defined a powerful signature to predict overall survival.
Direct CD32 T-cell cytotoxicity: implications for breast cancer prognosis and treatmentCD32-chimeric receptor T cell identifies CD32 cell surface ligand(s), on breast cancer (BC) cells, leading to BC cell elimination in vitro and in vivo and allowing detection of genes prognostically relevant.
VEGFR3 modulates brain microvessel branching in a mouse model of 22q11.2 deletion syndromeThis study provides genetic evidence that VEGFR3 regulates vessel branching and filopodia formation in the embryonic mouse brain and is a likely mediator of brain vessel anomalies in Tbx1 mutant mice.
Aerocyte specification and lung adaptation to breathing is dependent on alternative splicing changesPerinatal cell type–specific alternative splicing changes modulate the intercellular communication between alveolar epithelial AT1 and endothelial cells, leading to the specification of aerocytes, a specialized type of alveolar capillary ECs critical for gas exchanges.
High-resolution structure of a fish aquaporin reveals a novel extracellular foldThe structural and functional characterization of a fish AQP reveals a water-specific AQP with unique structural features that may have implications for channel gating in response to osmotic changes.
Autoimmune RNA dysregulation and seizures: therapeutic prospects in neuropsychiatric lupusLupus autoantibodies directed at neuroregulatory BC200 RNA cause seizure susceptibility in mice, but sequestration with antigen prevents seizures, indicating utility in therapeutic interventions.
Whole-exome sequencing of epithelial ovarian carcinomas differing in resistance to platinum therapyExploration of the prognostic and predictive significance of exome variation in epithelial ovarian carcinoma patients, with TP53, Hippo, homologous recombination genes, and the SBS6 signature as the most interesting results.
Methods
Measuring cystic fibrosis drug responses in organoids derived from 2D differentiated nasal epitheliaThis work describes an optimized assay to determine CFTR drug responses in people with cystic fibrosis, using nasal-airway organoids that are generated from 2D differentiated epithelial monolayers.
Resources
Improving the computation efficiency of polygenic risk score modeling: faster in JuliaTo enable computationally efficient polygenic risk score (PRS) calculations, PRS.jl translates a field standard PRS construction method, PRS-CS, to the Julia programming language.
Islet Gene View—a tool to facilitate islet researchIslet Gene View (IGW) is a web resource that makes information on gene expression in human islets from donors easily accessible to the scientific community. The relationship of global RNA expression from 188 donor-islets with islet phenotypes is explored.
