Browse Articles

Cytosolic acetyl-coenzyme A is a signalling metabolite to control mitophagy

Plastic mulch productivity-sustainability tradeoffs and pathways toward an eco-friendly framework: insights from a global meta-analysis

Reversible bismuth reduction-driven dark photoelectrochemistry

Early hominins from Morocco basal to the Homo sapiens lineage

Abstract Palaeogenetic evidence suggests that the last common ancestor of present-day humans, Neanderthals and Denisovans lived around 765–550 thousand years ago (ka) 1 . However, both the geographical distribution and the morphology of these ancestral humans remain uncertain. The Homo antecessor fossils from the TD6 layer of Gran Dolina at Atapuerca, Spain, dated between 950 ka and 770 ka (ref.  2 ), have been proposed as potential candidates for this ancestral population 3 . However, all securely dated Homo sapiens fossils before 90 ka were found either in Africa or at the gateway to Asia, strongly suggesting an African rather than a Eurasian origin of our species. Here we describe new hominin fossils from the Grotte à Hominidés at Thomas Quarry I (ThI-GH) in Casablanca, Morocco, dated to around 773 ka. These fossils are similar in age to H. antecessor , yet are morphologically distinct, displaying a combination of primitive traits and of derived features reminiscent of later H. sapiens and Eurasian archaic hominins. The ThI-GH hominins provide insights into African populations predating the earliest H. sapiens individuals discovered at Jebel Irhoud in Morocco 4 and provide strong evidence for an African lineage ancestral to our species. These fossils offer clues about the last common ancestor shared with Neanderthals and Denisovans.

CDK2 inhibitor BLU-222 synergizes with CDK4/6 inhibitors in drug resistant breast cancers through p21/p27 induction

Dynamic single-cell transcriptomics reveals lsamp-guided neural network formation in male S. japonicum driving female reproduction

Resurrected nitrogenases recapitulate canonical N-isotope biosignatures over two billion years

Camouflaged nanorobots target and regulate macrophage subcellular organelle crosstalk patterns to promote neural regeneration

A common DNA deletion altering the 3’UTR of mdr1 is associated with reduced mefloquine susceptibility in P. vivax parasites from Cambodian patients

Biophysical characterization of Eag chaperones suggests the mechanism of effector transmembrane domain release

Abstract The type VI secretion system (T6SS) is a dynamic protein nanomachine found in Gram-negative bacteria that secretes toxic effectors into prey-cells. For secretion, effectors require chaperones or adaptors for proper loading onto the T6SS. Effector associated genes (Eags) are a family of T6SS chaperones that stabilize N-terminal transmembrane domains (TMDs) found in thousands of effectors. Eags are essential for secretion and inhibit effector TMDs from prematurely adopting a membrane-penetrative conformation. However, the mechanism of TMD release from its cognate Eag chaperone is unknown. Here, we take a biochemical and biophysical approach to probe the mechanism of TMD binding and dissociation from Eag chaperones. Using steady-state fluorescence, stopped-flow measurements, and bacterial competition assays, we compare the thermodynamics, kinetics, and in vivo chaperone function of wild-type and point variant Eag-TMD complexes. Additionally, we solve an X-ray crystal structure of an Eag-TMD point variant complex that captures an intermediate state of TMD release. Our data reveals the molecular features and specific residue contacts necessary for TMD binding and demonstrates the Eag conformational change required to initiate rapid release of the TMD. Overall, our work details the stability of Eag-TMD complexes and the energetic pathway for the dissociation of effector TMDs from their Eag chaperones.

Atypical pericapillary Ly6G⁺Nur77⁺ macrophages initiate type-2 immune responses to allergens in the mouse lung

Abstract The mechanisms of airway allergen sensing and type 2 immune response initiation remain poorly understood. Using a mouse house dust mite (HDM)-induced allergic airway model, we identify a population of lung macrophages located close to alveolar capillaries that express Ly6G and the nuclear receptor Nr4a1/Nur77. These atypical Ly6G + Nur77 + macrophages preferentially capture airway-delivered allergens and play an important role in initiating HDM-driven T helper type 2 (Th2) responses. They sense the major HDM allergen, the cysteine protease Der p 1, via protease-activated receptor 2 (PAR2), and their activation and accumulation require both PAR2 and Nr4a1/Nur77. These Ly6G + Nur77 + macrophages regulate the migration of conventional migratory dendritic cells (mDCs) to draining mediastinal lymph nodes (mLNs) through cysteinyl leukotriene (CysLT) production, which enhances mDC migration toward CCL21 for T cell priming. Inhibiting CysLT biosynthesis reduces mDC migration and dampens Th2 allergic responses, highlighting possible therapeutic avenues in type 2 immunity.

Chronic pain could be eased by uncoupling the sensory and emotional experiences

Asymmetrical covalent organic framework mixed matrix membranes for highly efficient gas separation

The simplest iminophosphane HPNH and its photoisomerization to aminophosphinidene H2NP

Assimilative causal inference

Hierarchical maturation of structural brain connectomes from birth to childhood

Harnessing Van Hove singularities for terahertz photoresponse via Fermi surface reconstruction in kagome lattices

Silencing lipid catabolism determines longevity in response to fasting

Abstract Oscillations between lipid anabolism and catabolism are essential for maintaining cellular health during metabolic fluctuations. Fasting, a conserved determinant of aging, improves disease outcomes and extends lifespan, yet the relative contributions of lipid catabolism versus its attenuation to fasting-induced longevity remain unresolved. The metabolic flexibility of C. elegans under variable nutrient availability provides a powerful system to address this question. We show that lifespan extension from fasting depends not on sustained activation of lipid catabolism, but on its silencing upon nutrient replenishment. The fasting-responsive nuclear hormone receptor NHR-49 activates β-oxidation; however, unlike classical ligand-regulated receptors, NHR-49 is regulated through ligand-independent mechanisms involving cofactor-mediated transcriptional attenuation and protein turnover. We identify casein kinase 1 alpha 1 (KIN-19) as a key regulator of metabolic plasticity and fasting-induced longevity that silences β-oxidation via primed phosphorylation of NHR-49. Thus, cooperative ligand-independent silencing of this conserved nuclear hormone receptor promotes fasting-associated longevity.

Architecture of the neutrophil compartment

Of all the quarries: Casablanca fossils reveal African ancestors of Homo sapiens