Table of Contents
Research Articles
- Lsd1 safeguards T-cell development via suppressing endogenous retroelements and interferon responses
Bulk and single-cell RNA-seq, combined with ChIP-seq analysis, reveal that the loss of Lsd1 leads to the aberrant depression of endogenous retroelements and subsequent IFN response signaling in thymocytes, which are possible causes of impaired early T cell development.
- The C-terminal tail of CSNAP attenuates the CSN complex
The study demonstrates inhibition of the COP9 signalosome (CSN) complex by a peptide derived from CSNAP, the smallest CSN subunit. The peptide displaces the endogenous CSNAP subunit from the complex, leading to a CSNAP null phenotype that attenuates CSN activity.
- Brain IGF-I regulates LTP, spatial memory, and sexual dimorphic behavior
A lack of brain-synthesized IGF-I almost completely abrogates hippocampal long-term potentiation (LTP), alters spatial memory and sex-dependent behavior, and produces major changes in the mouse hippocampal proteome.
- Extracellular matrix sensing via modulation of orientational order of integrins and F-actin in focal adhesions
Using fluorescence polarisation microscopy and computational modeling, we find that FA molecules exhibit ECM dependent orientational co-alignment or order. This molecular organizational property in addition to nanoscale localization may explain precise and sensitive decoding of ECM cues.
- Loss of polarity regulators initiates gasdermin-E-mediated pyroptosis in syncytiotrophoblasts
Disruption of atypical protein kinase-C isoforms leads to the initiation of pyroptosis, a form of programmed necrosis, in placental syncytiotrophoblasts at the human maternal–fetal interface.
- Catalytic mechanism of the zinc-dependent MutL endonuclease reaction
The catalytic mechanism for the DNA cleavage activity of the mismatch repair system endonuclease MutL has been identified, which provides a clue as to how cadmium inhibits its activity.
- Full-length transcript alterations in human bronchial epithelial cells with U2AF1 S34F mutations
Using long-read Nanopore cDNA sequencing, this study identifies full-length transcripts associated with U2AF1 S34F mutations revealing effects on translation regulation of specific genes.
- Reciprocal regulation between the molecular clock and kidney injury
The work describes the crosstalk between the circadian rhythm and kidney damage in several mouse genetic models defining that the molecular clock component Cry is important to regulate inflammation, metabolism, and fibrosis.
- Dispersal of PRC1 condensates disrupts polycomb chromatin domains and loops
Endogenous PRC1-mediated chromatin compaction and clustering of polycomb target loci is reversibly perturbed in mESCs by the addition of 1,6 hexanediol, which can disrupt biomolecular condensates.
- Gene-regulation modules in nonalcoholic fatty liver disease revealed by single-nucleus ATAC-seq
This study uncovers cell-type-specific global gene regulation in NAFLD progression, identifying core genes and shedding light on the disease’s molecular mechanisms.
- Human TLR8 induces inflammatory bone marrow erythromyeloblastic islands and anemia in SLE-prone mice
Human TLR8 induces an inflammatory phenotype in BM erythroblastic island central macrophages of lupus-prone Sle1.Yaa mice. Failure to support erythroid precursor adhesion and development induces fatal anemia caused by bone marrow failure followed by hemophagocytosis during stress erythropoiesis.
- Inhibition of protein arginine deiminase 4 prevents inflammation-mediated heart failure in arthritis
Inhibition of protein arginine deiminase 4 (PAD4), with an orally available inhibitor (JBI-589), prevents the development of hypertrophic cardiomyopathy and diastolic heart failure in murine inflammatory arthritis with reduced neutrophil infiltration, NET deposition, and biomarkers of thromboinflammation in the myocardium.
- Regulation of hPCL3 isoforms’ ubiquitination by TRIM21 in non-small cell lung cancer progression
hPCL3 isoforms, hPCL3S and hPCL3L, are studied in NSCLC. Elevated expression of both isoforms correlates with poor survival. Inhibiting hPCL3S reduces cell growth, invasion, and migration, suggesting it as a potential therapeutic target.
- ERK1/2-SOX9/FOXL2 axis regulates ovarian steroidogenesis and favors the follicular–luteal transition
ERK1/2 negatively regulates estradiol synthesis while positively regulating progesterone production in ovarian granulosa cells via the ERK1/2-SOX9/FOXL2 axis.
- Basonuclin-2 regulates extracellular matrix production and degradation
Basonuclin-2 (BNC2) is identified as a novel regulator of genes associated with the extracellular matrix and cytokines in fibroblasts. BNC2 is thereby identified as a novel regulator of the tumour microenvironment where its high expression correlates with poor prognosis.
- PRMT5 triggers glucocorticoid-induced cell migration in triple-negative breast cancer
In triple-negative breast cancer, PRMT5 functions as a master transcriptional coregulator of the glucocorticoid receptor regulating cell migration after dexamethasone treatment. PRMT5 acts in this case as a scaffolding protein independently of its catalytic activity to promote HP1g recruitment.
- RA-induced prominence-specific response resulted in distinctive regulation of Wnt and osteogenesis
Early exposure of RA induced altered expressions of Wnt-related genes and subsequent osteogenic differentiation in embryonic mouse craniofacial prominences in a spatiotemporal-dependent manner.
- Skewed X-inactivation is associated with retinal dystrophy in female carriers of RPGR mutations
This study shows that skewed X-inactivation modulates the occurrence of Retinitis Pigmentosa in female carriers of RPGR mutations. The findings have implications towards therapeutic interventions.
- Feto-maternal cholesterol transport regulated by β-Klotho–FGF15 axis is essential for fetal growth
Inter-tissue communication between β-Klotho in the yolk sac and fibroblast growth factor 15 in the embryo is required to regulate cholesterol supply from maternal blood to embryo through the yolk sac.
- Generating fast-twitch myotubes in vitro with an optogenetic-based, quantitative contractility assay
We here describe an in vitro contractility assay to control fiber-type composition in muscle cultures.
- HGF/c-Met/β1-integrin signalling axis induces tunneling nanotubes in A549 lung adenocarcinoma cells
Interactions between hepatocyte growth factor (HGF), the c-Met receptor, and β1-integrin induce tunneling nanotubes in A549 cells; paxillin and the downstream MAPK and PI3K pathways and the Arp2/3 complex drive HGF-induced TNT formation.
- IKBKB reduces huntingtin aggregation by phosphorylating serine 13 via a non-canonical IKK pathway
Early exposure of RA induced altered expressions of Wnt-related genes and subsequent osteogenic differentiation in embryonic mouse craniofacial prominences in a spatiotemporal-dependent manner.
- De novo network analysis reveals autism causal genes and developmental links to co-occurring traits
In this study, we provide a biological argument for looking at an autistic individual’s phenotype as being related to their combined genetic risk for different clusters of traits.
- Caspase-4 dimerisation and D289 auto-processing elicit an interleukin-1β-converting enzyme
The noncanonical inflammasome generates p32/p9 and p34/p9 active caspase-4 species via dimerisation and autocleavage; both species cleave GSDMD to induce pyroptosis, whereas p34/p9 matures IL-1β.
- High-resolution kinetic characterization of the RIG-I-signaling pathway and the antiviral response
This study takes a comprehensive approach to understand the dynamics of the cell-intrinsic response towards virus infection and how viruses actively modulate this.
- ATP-independent substrate recruitment to proteasomal degradation in mycobacteria
Mycobacterial proteasomes ensure survival during stress by recruiting substrates for degradation via ring-shaped activators. This study elucidates the mechanism of ATP-independent substrate recruitment through the bacterial proteasome activator (Bpa), revealing the determinants for substrate recognition and efficient degradation.
Resources
- Dissecting morphogenetic apoptosis through a genetic screen in Drosophila
This genetic screen identifies elements of the “morphogenetic apoptosis pathway” potentially involved in the regulation, the orchestration or the impact of the apoptotic process on morphogenesis.
Methods
- PASCAR: a multiscale framework to explore the design space of constitutive and inducible CAR T cells
An experimentally validated protein abundance structured population dynamic model for CAR T cells (PASCAR) that integrates processes from molecules to single cells to cell populations and systematically explores the design space of constitutive and tunable CAR T cells.
- Refining the genetic risk of breast cancer with rare haplotypes and pattern mining
A closed-pattern mining algorithm helps identify rare, noncontiguous haplotypes underlying breast cancer risk in British women in the UK Biobank.