BackgroundDisruption of cerebral energy metabolism is increasingly recognized as a key factor in the pathophysiology of mood disorders. Lactate, beyond its role as a metabolic byproduct, is now understood to be a critical player in brain energy homeostasis and a modulator of neuronal function. Recent advances in understanding lactate shuttling between astrocytes and neurons have opened new avenues

The cerebellar ventricular zone (VZ) is the primary source of progenitors that generate cerebellar GABAergic neurons, including Purkinje cells (PCs) and interneurons (INs). This study provides detailed characterization of human cerebellar GABAergic neurogenesis using transcriptomic and histopathological analyses and reveals conserved and unique features compared to rodents. We show that the sequential

Large-scale integration of microbattery systems on chips has long been hindered by the technical barrier between electrochemistry and microelectronics, particularly in terms of the compatibility of microbattery cells and their collective manufacturability. In this work, a silicon-based all-solid-state thin-film microbattery cell is developed at low temperatures for on-chip integration applications

The collective motion of epithelial cells is a fundamental biological process which plays a significant role in embryogenesis, wound healing, and tumor metastasis. While it has been broadly investigated for over a decade both in vivo and in vitro, large-scale coherent flocking phases remain underexplored and have so far been mostly described as fluid. In this work, we report an additional mode of large-scale

Structural homeostasis and proper distributions of signaling molecules in cilia require a constant flow of cargoes carried by intraflagellar transport (IFT) trains in both anterograde and retrograde directions within the thin, long ciliary shafts. In the motile cilium framework, the nine microtubule doublets of the same length serve as the transportation rails, and a preferential association to the

Brain oscillations in different behavioral states are essential for cognition, and oscillopathies contribute to cognitive dysfunction in neuropsychiatric diseases. Cannabis-1 receptor (CB1-R) activation was reported to suppress theta and fast gamma activities in rats during waking exploration, and here, we show that cannabis fundamentally alters network activity during sleep as well. Prominent theta

Understanding how localized brain interventions influence whole-brain dynamics is essential for deciphering neural function and designing therapeutic strategies. Using longitudinal functional MRI datasets collected from mice, we investigated the effects of focal interventions, such as thalamic lesions and chemogenetic silencing of cortical hubs. We found that these local manipulations disrupted the

Excitatory amino acid transporters (EAATs) reside on cell surfaces and uptake substrates, including L-glutamate, L-aspartate, and D-aspartate, using ion gradients. Among five EAATs, EAAT3 is the only isoform that can efficiently transport L-cysteine, a substrate for glutathione synthesis. Recent studies suggest that EAAT3 also transports the oncometabolite R-2-hydroxyglutarate (R-2HG). Here, we examined

The MRE11/RAD50/NBS1 (MRN) complex plays multiple roles in the maintenance of genome stability. MRN is associated with replication forks to preserve fork integrity and is also required for end resection at double-strand breaks (DSBs) to facilitate homologous recombination (HR). The critical need for proper control of the MRE11 nuclease activity is highlighted by the extensive nascent strand DNA degradation

Bestrophin-1 (BEST1) is a chloride channel expressed in the eye and other tissues of the body. A link between BEST1 and the principal inhibitory neurotransmitter γ -aminobutyric acid (GABA) has been proposed. The most appreciated receptors for extracellular GABA are the GABA B G-protein-coupled receptors and the pentameric GABA A chloride channels, both of which have fundamental roles in the central

Interdisciplinary research is essential for addressing complex global challenges, but there are concerns that scientific institutions like journals select against it. Prior work has focused largely on how interdisciplinarity relates to outcomes for published papers, but which papers get accepted for publication in the first place is unclear. Furthermore, journals may evaluate two key dimensions of

Pseudohypoparathyroidism type 1B (PHP1B) is a multihormone resistance disorder caused by aberrant GNAS methylation. Characteristic epigenetic changes at GNAS differentially methylated regions (DMRs), i.e., NESP, AS1, AS2, XL, and A/B, are associated with specific structural defects in different autosomal dominant PHP1B (AD-PHP1B) subtypes. However, mechanisms underlying abnormal GNAS methylation remain

Membrane frizzled-related protein (MFRP), present in the retinal pigment epithelium (RPE), is an integral membrane protein essential for ocular development and the normal physiology of the retina. Mutations in MFRP are associated with autosomal recessive nonsyndromic nanophthalmos, leading to severe hyperopia and early-onset retinitis pigmentosa. While several preclinical gene-augmentation and gene-editing

Spatial epigenomics and multiomics can provide fine-grained insights into cellular states but their widespread adoption is limited by the requirement for bespoke slides and capture chemistries for each data modality. Here, we present SPatial assay for Accessible chromatin, Cell lineages, and gene Expression with sequencing (SPACE-seq), a method that utilizes polyadenine-tailed epigenomic libraries

The elastic properties of nanoscale extracellular vesicles (EVs) are believed to influence their cellular interactions, thus having a profound implication in intercellular communication. However, accurate quantification of their elastic modulus is challenging due to their nanoscale dimensions and their fluid-like lipid bilayer. We show that the previous attempts to develop atomic force microscopy-based

We report a transition from the ferroelectric nematic liquid crystal (N F ) phase to a lower-temperature, apolar fluid phase having reentrant isotropic symmetry (I R ), in the liquid crystal compound RM734 doped with small concentrations of the ionic liquids 1-Butyl-3-methylimidazolium hexafluorophosphate (BMIM-PF 6 ) or 1-Ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (EMIM-TFSI). Even

Elevated miR-155 levels in B cell malignancies, such as CLL and DLBCL, correlate with increased aggressiveness of the disease. We recently reported that, in two different mouse models of miR-155 -driven B cell malignancy, miR-155 targets and down-regulates transcripts encoding ICOSL, the ligand for the Inducible T cell costimulator (ICOS), thereby impairing the capacity of T lymphocytes to recognize

Phospholipase Cβ (PLCβ) enzymes are the principal effectors activated by G q heterotrimers. Both Gα q and Gβγ subunits can activate PLCβ, which requires precise positioning of PLCβ at the plasma membrane to relieve structural autoinhibition and give the active site access to the phosphatidylinositol 4,5-bisphosphate (PIP2) substrate. PLCβ enzymes possess a unique distal C-terminal domain (dCTD) that

In order to forage for food, many animals regulate not only specific limb movements but the statistics of locomotor behavior, switching between long-range dispersal and local search depending on resource availability. How premotor circuits regulate locomotor statistics is not clear. Here, we analyze and model locomotor statistics and their modulation by attractive food odor in walking Drosophila .

Mitochondria are dynamic organelles that constantly change morphology. What controls mitochondrial morphology however remains unresolved. Using actively respiring yeast cells growing in distinct carbon sources, we find that mitochondrial morphology and activity are unrelated. Cells can exhibit fragmented or networked mitochondrial morphology in different nutrient environments independent of mitochondrial

Microbial ecosystems are commonly modeled by fixed interactions between species in steady exponential growth states. However, microbes in exponential growth often modify their environments so strongly that they are forced out of the growth state into stressed, nongrowing states. Such dynamics are typical of ecological succession in nature and serial-dilution cycles in the laboratory. Here, we introduce

Intussusceptive angiogenesis is an increasingly recognized vessel duplication process that generates and reshapes microvascular beds. However, the mechanism by which a vessel splits into two is poorly understood. Particularly vexing is formation of the hallmark transluminal endothelial cell bridge. How an endothelial cell comes to cross a flowing lumen rather than line it is enigmatic. To elucidate

Conjugation, the major driver of the spread of antimicrobial resistance genes, relies on a conjugation pilus for DNA transfer. Conjugative pili, such as the F-pilus, are dynamic tubular structures, composed of a polymerized pilin, that mediate the initial donor–recipient interactions, a process known as mating pair formation (MPF). IncH are low-copy-number plasmids, traditionally considered broad host

Preparing to rapidly respond to emerging infectious diseases is critical. SpillOver: Viral Risk Ranking is an open-source tool developed to assess the risk of novel wildlife-origin viruses spilling over from animals to humans and spreading in human populations. Several risk factors used by the tool depend on evidence of previous zoonotic spillover itself or sustained transmission in humans. Therefore

Slow-wave sleep (SWS) and rapid eye movement sleep are the two primary components of electrophysiological sleep (e-sleep) in mammals and birds. Slow waves in the cortex not only characterize SWS but are also used as biological markers for sleep homeostasis, given their rebound after sleep deprivation (SD). Recently, it has been reported that the Australian dragon Pogona vitticeps exhibits a two-stage

Influenza viruses are enveloped, negative-sense single-stranded RNA viruses covered in a dense layer of glycoproteins. Hemagglutinin (HA) accounts for 80 to 90% of influenza glycoprotein and plays a role in host cell binding and membrane fusion. While previous studies have characterized structures of purified receptor-free and receptor-bound HA, the effect of receptor binding on HA organization and

TonB-dependent signal transduction is a versatile mechanism observed in gram-negative bacteria that integrates energy-dependent substrate transport with signal relay. In Escherichia coli , the TonB–ExbBD motor complex energizes the TonB-dependent outer membrane transporter FecA, facilitating ferric citrate import. FecA also acts as a sensor, transmitting signals to the cytoplasmic membrane protein

Crop pathogens often lack exclusive access to their host and must interact with plants concurrently engaged with numerous other symbionts. Here, we demonstrate that the colonization of hosts by plant–mutualistic mycorrhizal fungi can indirectly induce transcriptional responses of a major plant parasite, the nematode Globodera pallida , via a modified host resource profile. A shift in the resource profile

Neutrophils are the most abundant circulating leukocyte population that play critical roles in neuroinflammation following central nervous system (CNS) injury. CD177, a glycoprotein on neutrophils, is emerging as an important immune regulator which can fundamentally affect multiple human inflammatory diseases. However, the role and regulatory mechanism of CD177 glycobiology of neutrophils in neuroinflammation

Mechanical snapping instabilities are leveraged by natural systems, metamaterials, and devices for rapid sensing, actuation, and shape changes, as well as to absorb impact. In all current forms of snapping, shapes deform in the same direction as the exerted forces, even though there is no physical law that dictates this. Here, we realize countersnapping mechanical structures that respond in the opposite

Elevated brain levels of the essential metals manganese (Mn), copper, or iron induce motor disease. However, mechanisms of metal-induced motor disease are unclear and treatments are lacking. Elucidating the mechanisms of Mn-induced motor disease is particularly important because occupational and environmental Mn overexposure is a global public health problem. To address this, here we combined unbiased

Mitochondrial DNA (mtDNA) replication requires a steady supply of deoxyribonucleotides (dNTPs), synthesized de novo by ribonucleotide reductase (RNR). In nondividing cells, RNR consists of RRM1 and RRM2B subunits. Mutations in RRM2B cause mtDNA depletion syndrome, linked to muscle weakness, neurological decline, and early mortality. The impact of RRM2B deficiency on dNTP pools in nondividing tissues

Crops genetically engineered to produce insecticidal proteins from the bacterium Bacillus thuringiensis (Bt) have been used extensively to control some major crop pests, but their benefits decrease when pests evolve resistance. Better understanding of the genetic basis of resistance is needed to effectively monitor, manage, and counter pest resistance to Bt crops. Resistance to Bt proteins in at least

Forming and forgetting memories shape our self-awareness and help us face future challenges. Therefore, understanding how memories are formed and how different memories interact in the brain is important. Previous studies have shown that thirsty flies sense humidity through ionotropic receptors, which help them locate water sources. Here, we showed that thirsty flies can be trained to associate specific

Ischemic retinal diseases are major causes of blindness worldwide and are characterized by pathological angiogenesis. Epigenetic alterations in response to metabolic shifts in endothelial cells (ECs) suffice to underlie excessive angiogenesis. Lactate accumulation and its subsequent histone lactylation in ECs contribute to vascular disorders. However, the regulatory mechanism of establishing and sustaining

Although cochlear implants (CIs) provide valuable auditory information to more than one million profoundly deaf patients, these devices remain inadequate in conveying fine timing cues. Early deaf patients in particular struggle to use interaural time differences (ITDs) for spatial hearing and auditory scene analysis. Why CI patients experience these limitations remains controversial. One possible explanation

Cellular signaling processes can elicit powerful responses and may need to be amplified to be efficient or dampened to prevent overstimulation. Therefore, they often involve autoregulatory feedbacks. Receptor kinase signaling pathways are abundant in plants, where they convey the presence of both exogenous and endogenous ligands. Among them, endogenous CLAVATA3/EMBRYO SURROUNDING REGION (CLE) peptide

Awareness of the threats of climate change is causing distress in increasingly documented ways, with youth particularly affected. Experiences such as climate distress and eco-anxiety have implications for the health and well-being of societies and economies, including individuals’ mental health and future planning, as well as their agency beliefs. Here, we show in a large sample of US youth (n = 2

Bedaquiline is the cornerstone of a new regimen for the treatment of drug-resistant tuberculosis. However, its clinical use is threatened by the emergence of bedaquiline-resistant strains of Mycobacterium tuberculosis . Bedaquiline targets mycobacterial ATP synthase but the predominant route to clinical bedaquiline resistance is via upregulation of the MmpS5L5 efflux pump due to mutations that inactivate

There is broad consensus that AI presents risks, but considerable disagreement about the nature of those risks. These differing viewpoints can be understood as distinct narratives, each offering a specific interpretation of AI’s potential dangers. One narrative focuses on doomsday predictions of AI posing long-term existential risks for humanity. Another narrative prioritizes immediate concerns that

The 2024 Nobel Prize in Physics recognizes breakthroughs contributing to the emergence of a new understanding of the computations that underlie human intelligence, with profound implications for artificially intelligent systems. John Hopfield and Geoffrey Hinton played seminal roles in these breakthroughs. I begin by characterizing the scientific context in which the new understanding of intelligence

Herpesviruses encode conserved protein kinases (CHPKs) that target cellular cyclin-dependent kinase (CDK) phosphorylation sites; thus, they are termed viral CDK-like kinases. Tyrosine 15 in the GxGxxG motifs of CDK1 and CDK2, whose phosphorylation down-regulates their catalytic activities, is conserved in the corresponding motifs of CHPKs. We found that CHPK UL13, the corresponding Tyr-162 in herpes