Proceedings of the National Academy of Sciences
Articles in this Issue
Unveiling Cas8 dynamics and regulation within a transposon-encoded Cascade–TniQ complex
The Vibrio cholerae Cascade–TniQ complex unveiled a new paradigm in biology, demonstrating that CRISPR-associated proteins can direct DNA transposition. Despite...
Structural basis for neutralizing antibody binding to pertussis toxin
Pertussis toxin (PT) is a key protective antigen in vaccine- and natural immunity-mediated protection from Bordetella pertussis infection. Despite its importanc...
Digital phenotyping using smartphones could help steer mental health treatment
DDX54 downregulation enhances anti-PD1 therapy in immune-desert lung tumors with high tumor mutational burden
High tumor mutational burden (TMB-H) is a predictive biomarker for the responsiveness of cancer to immune checkpoint inhibitor (ICI) therapy that indicates whether immune cells can sufficiently recogn...
Phosphatidylinositol 4,5-bisphosphate activation mechanism of human KCNQ5
The human voltage-gated potassium channels KCNQ2, KCNQ3, and KCNQ5 can form homo- and heterotetrameric channels that are responsible for generating the neuronal M current and maintaining the membrane...
Nuclear Galectin-1 promotes <i>KRAS</i> -dependent activation of pancreatic cancer stellate cells
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers, primarily due to its complex tumor microenvironment (TME), which drives both disease progression and therapy resistance....
A conserved ARF–DNA interface underlies auxin-triggered transcriptional response
Auxin Response Factor (ARF) plant transcription factors are the key effectors in auxin signaling. Their DNA-Binding Domain (DBD) contains a B3 domain that allows base-specific interactions with Auxin...
Phenotypic changes of auditory nerve fibers after excitotoxicity
There is a substantial body of evidence elucidating the pathophysiological aspects of excitotoxicity in the mammalian cochlea. However, the question of whether the resultant damage is reversible remai...
Reply to Falkingham et al.: Trackway shows flap-running in feathered dinosaurs
Reply to Brown et al.: Significant sex differences in accelerated cortical thinning associated with the COVID-19 lockdowns
Lenacapavir disrupts HIV-1 core integrity while stabilizing the capsid lattice
Lenacapavir (GS-6207; LEN) is a potent HIV-1 capsid inhibitor approved for treating multidrug-resistant infection. LEN binds to a hydrophobic pocket between neighboring capsid (CA) proteins in hexamer...
Lung B cells in ectopic germinal centers undergo affinity maturation
The lungs are constantly exposed to the external environment and a myriad of antigenic challenges within the air. Chronic exposure to allergens and other airborne antigens can result in the formation...
Reconfigurable homochiral colloidal clusters assembled under orthogonally applied electric and magnetic fields
Chiral structures assembled from colloids are of great interest for applications in metamaterials and micromachines. However, similar to their molecular counterparts, these assemblies often result in...
The cingulate cortex facilitates auditory perception under challenging listening conditions
We often exert greater cognitive resources (i.e., listening effort) to understand speech under challenging acoustic conditions. This mechanism can be overwhelmed in those with hearing loss, resulting...
No compelling evidence of sex differences in brain maturation during COVID-19 lockdowns when the sexes are compared statistically
<i>LMX1B</i> missense-perturbation of regulatory element footprints disrupts serotonergic forebrain axon arborization
Pathogenic coding mutations are prevalent in human neuronal transcription factors (TFs) but how they disrupt development is poorly understood. Lmx1b is a master transcriptional regulator of postmitoti...
Quirks of track preservation and formation are more likely than pre-avian flight and ultrafast dinosaurs
Reactivation of memory-associated neurons induces downstream suppression of competing neuronal populations
Inducing apparent memory recall by tagging and optogenetically reactivating cells in the hippocampus was demonstrated over a decade ago. However, the hippocampal dynamics resulting from this reactivat...
Design of a halogen bond catalyzed DNA endonuclease
In this study, we expand the repertoire of biological catalysts by showing that a halogen bond (X-bond) can functionally replace the magnesium (Mg 2+ ) cofactor...
Prolonged signaling of backbone-modified glucagon‐like peptide‐ <b>1</b> analogues with diverse receptor trafficking
Signal duration and subcellular location are emerging as important facets of G protein–coupled receptor (GPCR) function. The glucagon-like peptide-1 receptor (GLP-1R), a clinically relevant class B1 G...
The TRPV3 channel is a mediator of zinc influx and homeostasis in murine oocytes
Zinc (Zn 2+ ) homeostasis is essential for gametogenesis and reproduction, and its deficiency causes infertility. Oocytes contain higher Zn...
Following phospholipid transfer through the OmpF <sub>3</sub> –MlaA–MlaC lipid shuttle with native mass spectrometry
The maintenance of lipid asymmetry (Mla) system in gram-negative bacteria transfers phospholipids between the outer and inner membrane to maintain the outer membrane asymmetry. Misplaced phospholipids...
Signaling networks in cancer stromal senescent cells establish malignant microenvironment
The tumor microenvironment (TME) encompasses various cell types, blood and lymphatic vessels, and noncellular constituents like extracellular matrix (ECM) and cytokines. These intricate interactions b...
PHLPP2 is a pseudophosphatase that lost activity in the metazoan ancestor
The phosphoinositide 3-kinase (PI3K) pathway is a major regulator of cell and organismal growth. Consequently, hyperactivation of PI3K and its downstream effector kinase, Akt, is observed in many huma...
Childhood muscle growth: Reference curves for lower leg muscle volumes and their clinical application in cerebral palsy
Skeletal muscles grow substantially during childhood. However, quantitative information about the size of typically developing children’s muscles is sparse. Here, the objective was to construct muscle...