New papers on Cell & molecular biology
120 new papers on cell & molecular biology in the last 7 days, within Biology. These are the 50 Pipette rates most worth reading, with the main result in the authors' own words.
The best of the week
Mammals produce cyclo -octasulfur to suppress lipid peroxidation and ferroptosis
Together, these findings reveal an endogenous pool of S 8 in mammals that may protect cells from oxidative membrane damage by modulating cellular sensitivity to ferroptosis.
Peer-reviewed journalClaims a big stepReal-world useStress triggers global histone synthesis in the liver
However, multiple systemic and liver-specific stresses induce a previously uncharacterized surge of hepatocyte nucleosome production that is uncoupled from DNA replication.
PreprintClaims a big stepOrthogonal Chemical Proteomic Strategies Reveal the Cholesteryl Ester Interactome in Mammalian Cells
Collectively, this work provides the first systems-level map of CE-protein interactions and establishes a generalizable, multimodal framework for chemically resolving lipid-protein interactomes.
PreprintClaims a big stepMapping the human sperm proteome across compartments, donors and individual cells
Here we present the deepest proteomic atlas of human spermatozoa to date, identifying 10,828 proteins across six donors.
PreprintA phytocannabinoid-sensitive phosphorylation switch converts endocannabinoids into alternative lipid GPCR activators
Here, we show that phosphorylation of biologically important anandamide generates naturally occurring anandamide phosphate (AEAp), which switches GPCR ligand specificity to lysophosphatidic acid (LPA) receptors (LPARs) and the primate-specific bile acid sensory receptor MRGPRX4.
PreprintRedox activation of ATG5 licenses autophagy upon nutrient restriction
The autophagic response to nutrient restriction is thus gated by oxidation of a single cysteine.
PreprintProtein hunger-driven nitrogen flow from phospholipids to amino acids inDrosophila
Using Drosophila, we reveal a previously undocumented nitrogen flow from phospholipids to amino acids, a process enhanced by protein deprivation.
PreprintIn-cell structures visualize human pre-ribosome assembly in the nucleolus
Here, we used cryogenic correlative light and electron tomography to visualize molecular landscapes within HeLa cell nucleoli and obtained in-cell structural snapshots of both ribosomal subunit precursors, the SSU processome and the pre-60S.
Peer-reviewed journalClaims a big stepExtending single-cell proteomics from HeLa to small primary human immune cells
Here, we establish a high-sensitivity, label-free SCP platform that extends current depth and reproducibility.
Peer-reviewed journalThe nematode Caenorhabditis elegans has a cationic amphiphilic drug (CAD) defense system
Through a forward genetic screen and mining of published datasets, we discovered that CADs induce the expression of the CYP-35B family of cytochrome P450s and the PGP-13 p-glycoprotein pump via the nuclear receptors NHR-70 and NHR-107 in the nematode C. elegans.
Peer-reviewed journalReal-world useThe heart-liver axis controls platelet turnover by hepatic STAT3 phosphorylation and TPO regulation after acute myocardial infarction
Results: Here, we identify a heart-liver axis that dynamically regulates platelet production post AMI.
PreprintA global S-palmitoylation map of Trypanosoma cruzi identifies ABCA10 as a key component of a redundant heme-acquisition system
Together, these findings reveal a redundant heme-scavenging strategy and expose a druggable vulnerability in a neglected pathogen.
Peer-reviewed journalReal-world useThe kinetoplastid-specific transcription factor mtTF1 is essential for mitochondrial gene expression and maxicircle replication in Trypanosoma brucei
This study identifies and characterizes the first mitochondrial transcription factor (mtTF1, Tb927.6.4510) in the Kinetoplastea.
Peer-reviewed journalGhost Neuron preparation unlocks high-resolution structural mapping of intracellular architecture in axons
Here, we introduce the Ghost Neuron technique, a preparation combining brief hypotonic treatment with controlled mechanical rupture immediately before freezing, facilitating high-contrast imaging of neuronal ultrastructure within its neurite topology.
Peer-reviewed journalRecursive feedback between Piezo1 conformation and membrane mechanics drives self-organization into finite clusters
Here we identify a membrane-feedback mechanism that converts single-channel mechanosensing into self-organized Piezo1 clusters.
PreprintPolymer Polydispersity and Lipid Composition Control Nanoplastic Disassembly in Membranes
These results identify the molecular-weight distribution as a key determinant of nanoplastic-membrane interactions, and indicate that uniform model particles underestimate the release of polymer chains into biological membranes.
PreprintMitochondrial dynamics resolve physical-social tensions and challenges through adaptable multi-objective optimisation
We show that wildtype Arabidopsis mitochondrial dynamics near-optimally resolve a tradeoff between maintaining physical spacing and supporting biomolecular exchange.
PreprintBold claims, read criticallyGDF3 is an endogenous antagonist of the ActE-ALK7/ACVR2 pathway in adipocytes
We identify GDF3, a TGF-{beta} superfamily ligand upregulated in obese adipose tissue, as the principal endogenous antagonist of ActE/ALK7 signaling.
PreprintReal-world useNEAT1_1 -encoded microprotein PSNEAT1 drives rDNA transcription via phase separation with WRN
Collectively, our study reveals an LLPS-dependent mechanism by which the NEAT1_1 -encoded microprotein PSNEAT1 regulates nucleolar structure and function.
Peer-reviewed journalCdk1 heterozygosity triggers premeiotic endoreplication and unreduced sperm formation via the Cdk2/Ccne1–Fzr1a pathway in loach, a teleost
Here, we reported that heterozygous mutation of cdk1 in the loach, Misgurnus anguillicaudatus (Teleostei, Cobitidae), triggered premeiotic endoreplication in spermatogonia, resulting in the production of unreduced diploid sperms.
Peer-reviewed journalBold claims, read criticallyReal-world useNetwork topology creates independent control of multiple checkpoints in the cell cycle system
This paper mathematically demonstrates that “modularity,” where parts of a system are controlled independently of others, arises solely from network topology.
Peer-reviewed journalCoherence in Biological Systems
We propose that coherence provides a physical description of this transition.
PreprintBold claims, read criticallyTargeting PFKFB3 Metabolic Gatekeeping of β-Cell Dysfunctional States Enables Durable Glucose Tolerance in Type 2 Diabetes
These findings establish PFKFB3 inhibition as a potential disease-modifying therapeutic strategy for T2D.
PreprintBold claims, read criticallyReal-world useHigh-throughput label-free single-cell proteomics enabled by multicolumn NanoLC
Here, we present a multicolumn nanoLC–MS platform that achieves 5-minute separation windows with 100% duty cycles at ~100 nL/min, enabling the analysis of up to 288 single cells per day.
Peer-reviewed journalBold claims, read criticallyA designed ubiquitin-binding protein selectively enriches and visualizes unanchored ubiquitin
To address this, we used high-throughput affinity maturation and computational protein design to engineer novel proteins that selectively bind unanchored ubiquitin.
Peer-reviewed journalEndogenous subthreshold noise and PIP2 tune diastolic coherence across the intact sinoatrial node through stochastic resonance
Pacemaking is therefore graded by a bioenergetic supply chain that sets the noise, not by entrainment alone.
PreprintSingle Amino Acid Disease Mutations Act as Genetic Glues to Drive Neo-substrate Degradation
Unexpectedly, we identify single amino acid substitutions that create functional short linear motif degrons to drive targeted protein degradation independently of protein quality control.
PreprintBold claims, read criticallyLymphatic ERG Governs Junctional Plasticity and Fluid Clearance via an EDNRB Signaling Axis in Pulmonary Fibrosis
Here, we demonstrate that the lineage-defining transcription factor ERG in lymphatic endothelial cells (LECs) governs junctional plasticity and fluid drainage in pulmonary fibrosis.
PreprintSelective depletion of upper-layer somatostatin interneuron subtypes in schizophrenia
Second, we find reduced abundance (depletion) of a subset of upper-layer Sst interneurons and increased abundance of L6b excitatory neurons, with both changes confirmed in spatial transcriptomics (12 controls, 12 SCZ).
PreprintHost membrane cholesterol constrains constitutive signaling of the oncogenic KSHV GPCR ORF74
Here, we identify a previously unrecognized cholesterol-dependent allosteric mechanism by which the oncogenic Kaposi's sarcoma-associated herpesvirus (KSHV) GPCR ORF74 constrains its constitutive activity.
PreprintRobust High-Throughput Flickering Spectroscopy for Measurements of Red Blood Cell Membrane Mechanics
In combination with an automated imaging system it is possible to measure thousands of cells in one day, with no user input.
PreprintAcid Stress-induced plasma membrane ceramide arises from lysosome-plasma membrane fusion
Using this inducer, we defined a lysosome-to-plasma membrane pathway for stress-induced PMCer generation.
PreprintActive control of surface immobilization in the foraging behavior of Paramecium
With long term behavioral tracking, we show that this variable behavior is a component of Paramecium's foraging behavior in the presence of bacteria, where the organism alternates between exploring and stopping on surfaces to feed.
PreprintVariant-Specific Rewiring of Lysosomal Positioning by STARD9 Produces Opposite Cholesterol Trafficking Outcomes
We identify STARD9, a lysosomal cholesterol-sensing kinesin, as a causal gene for divergent familial dyslipidemias and premature atherosclerosis.
PreprintBold claims, read criticallyReal-world usePhosphoregulation of hierarchical protein condensate formation during clathrin-mediated endocytosis
Collectively, this work establishes a two-stage model of protein condensation that drives CME progression from initiation to maturation and offers a general framework for how protein phosphorylation dynamically modulates biomolecular condensation in vivo.
PreprintWound-induced syncytia outpace mononucleate neighbors during Drosophila wound repair
Syncytia use several routes to speed wound repair: they outpace diploid cells at the wound margin to lead the initial resealing of the wound; they reduce the need for intercalation as the tissue reshapes during closure; and they pool resources of their component cells to concentrate them toward the wound margin.
Peer-reviewed journalStromal CTHRC1 protects the valvular interstitium from macrophage-associated inflammatory remodeling and calcification
These findings indicate that transient CTHRC1 induction after endothelial injury defines an endogenous stromal protective response that preserves the valvular interstitial microenvironment and limits macrophage-associated tissue injury and subsequent dystrophic calcification.
PreprintGPR182 promotes atherosclerosis via facilitating arterial lipid deposition
Here, we identify GPR182, a recently characterized lipoprotein receptor of the atypical chemokine receptor family, as a key mediator of lipid deposition in the aortic endothelium during atherosclerosis.
PreprintReal-world useEndocytosis and Compartmentalized Intracellular Signaling of the Prostaglandin Receptor EP4 Mediate Pain
Here, we show that pain-like responses evoked by PGE2 in dorsal root ganglion (DRG) nociceptors are mediated by internalization and compartmentalized signaling of the EP4 receptor.
PreprintShort-term memory of past caspase activity biases cell elimination in vivo
We outline the central role of past exposure to sublethal caspase activity, which sensitises cells to apoptosis for several hours and reduces their threshold, and can bias single-cell elimination.
Peer-reviewed journalMultimodal 3D imaging reveals a central role for lysosomes indissolution of cholesterol crystals by macrophages
Together, our findings highlight the lysosomal pathway as responsible for dissolution of CCs, cholesterol trafficking, and efflux in macrophages.
PreprintPathogen subversion of neuro-epidermal signaling impairs lysosomal function to disrupt collagen homeostasis in Caenorhabditis elegans
Our study reveals a neuro-epidermal axis wherein pathogens exploit neuronal signals to disrupt lysosomal function and collagen homeostasis, identifying NSIF-1 and ELT-3 as potential targets to counteract infection-driven ECM dysregulation.
Peer-reviewed journalCellular remodeling during reversible life-stage transition in sessile ciliates: Genomic and transcriptomic insights
Ultimately, our findings highlight how ciliates integrate global transcriptomic shifts with organelle-specific spatial and metabolic fine-tuning to meet the precise mechanical requirements of complex life-cycle transitions.
Peer-reviewed journalClade B serpins promote direct basal-to-goblet cell differentiation in airways of patients with chronic obstructive pulmonary disease
Together, these results indicate clade B serpins contribute to altered epithelial differentiation and inflammatory signaling in COPD and support therapeutic targeting of clade B serpins to reduce GCH.
PreprintReal-world useTaxane-induced conformational changes in the microtubule lattice activate GEF-H1-dependent RhoA signalling
Here we show that taxanes activate RhoA signalling and induce actin remodelling by releasing the RhoA activator GEF-H1 from microtubules.
Peer-reviewed journalCell-free membrane systems reveal electrostatic control of ion transport in TMEM165 and disease-associated CaCA2 variants
More broadly, this work establishes a strategy for reconstructing organellar membrane proteins, resolving disease mechanisms, and engineering transport function in defined synthetic systems.
PreprintBold claims, read criticallySingle residues within the YTHDF intrinsically disordered region control m6A-dependent mRNA decay
These findings define the residue-level regulatory logic of the YTHDF2 IDR and establish base-editor screening as a strategy to uncover functional mechanisms encoded within IDR regions.
PreprintParental B-MYB/FOXM1 controls mitotic E2F to determine daughter cell fate
Thus, B-MYB/FOXM1 governs a tri-directional (G2 restriction point) where cells commit to continued cycling through early B-MYB/FOXM1 activation; cell-cycle exit through delayed B-MYB/FOXM1 activation; or mitotic bypass by B-MYB/FOXM1 inactivation.
PreprintFlow, dynamics and active fracture in hydraulic multicellular systems
Here, we develop a theoretical approach that captures cellular mechanics and fluid flow in one framework.
PreprintBold claims, read criticallyA repair-associated bronchial epithelial differentiation trajectory through KRT14+ basal and hillock-like cells drives airway inflammation and remodelling in childhood-onset asthma
We identify a novel asthma-associated non-canonical epithelial differentiation trajectory in which a repair-associated KLF4+ basal cell subset differentiates into KRT13+ hillock-like cells through a proliferative KRT14+ intermediate.
Preprint