eLife

During zygotic genome activation in Drosophila , broad domains of Polycomb-modified chromatin are rapidly established across the genome. Here, we investigate the spatial and temporal dynamics by which Polycomb group (PcG) histone modifications, H3K27me3 and H2Aub, emerge during early embryogenesis. Using ChIP-seq and live imaging of CRISPR-engineered GFP-tagged PcG components, we show that PRC2-d…

Expression of the G protein coupled receptor GPR34 is highly enriched in microglia and has been reported to be downregulated in several brain disease contexts, including Alzheimers disease (AD) and multiple sclerosis (MS). GPR34 function is poorly understood, as is its role in regulation of microglial states. Using RNA-sequencing, we find that microglia from Gpr34 knockout (KO) mouse brains exhib…

The mating behavior of nocturnal Manduca sexta hawkmoths is under strict temporal control. It is orchestrated via circadian and ultradian oscillations in sex-pheromone stimuli as social Zeitgeber. The extremely sensitive pheromone-detecting olfactory receptor neurons (ORNs) that innervate the long trichoid sensilla on the male’s antennae are peripheral circadian clocks. They express the transcrip…

Non-invasive recordings using brain electrophysiology provide credible insights into decline in neuronal functioning with age. New approaches are required to translate these results into compelling clinical metrics and meet the global challenge of preserving brain health in ageing. Changes in neuronal dynamics with ageing are observable in the power spectra of EEG and MEG recordings. Highly promi…

Certain areas of the brain involved in episodic memory and behavior, such as the hippocampus, express high levels of insulin receptors and glucose transporter-4 (GLUT4) and are responsive to insulin. Insulin and neuronal glucose metabolism improve cognitive functions and regulate mood in humans. Insulin-dependent GLUT4 trafficking has been extensively studied in muscle and adipose tissue, but lit…

Nitric oxide (NO) produced by nitric-oxide synthase (NOS) is a key regulator of animal physiology. Here we uncover a function for NO in the integration of UV exposure and the gating of a UV-avoidance circuit. We studied UV/violet avoidance mediated by brain ciliary photoreceptors (cPRCs) in larvae of the annelid Platynereis dumerilii. In the larva, NOS is expressed in interneurons (INNOS) postsyn…

Few concepts are as central to evolution as is fitness, and yet the quantification of fitness is often ambiguous. In particular, high-throughput experiments to measure mutant fitness in microbes are increasingly common but vary widely in their definitions of fitness, which makes their results difficult to compare. What are the consequences of these different fitness statistics, and is there a bes…

Discovering biochemical circuits that exhibit a desired behavior is an outstanding problem in biological engineering. The traditional approach of enumerating every possible circuit topology becomes intractable for circuits with more than four components due to combinatorial scaling of the search space. Here, we use Monte Carlo Tree Search (MCTS), a reinforcement learning (RL) algorithm, to optimi…

Although the causal association between aging and osteoarthritis (OA) has been documented, our understanding of the underlying mechanism remains incomplete. To define the regulatory molecules governing chondrocyte aging, we performed transcriptomic analysis of young and old human chondrocytes from healthy donors. The data predicted that GATA-binding protein 4 (GATA4) may play a key role in mediat…

Defining quantitative biochemical mechanisms of microtubule dynamics and regulation is a current challenge. Stu2/XMAP215-family polymerases use tubulin-binding TOG domains to catalyze microtubule growth, but how polymerase activity results from the number and tubulinbinding properties of TOGs is not understood. We tested whether an enzyme-like biochemical model for the unrelated actin polymerase …

Vector-borne, protist parasites have evolved complex developmental programs to adapt to very distinct host environments. How these important pathogens transition between insect and mammalian stages is only poorly understood. Here we investigate stage differentiation in the trypanosomatid parasite Leishmania that shows constitutive gene transcription, thus providing a unique model system to assess…

Social hierarchies structure groups and confer advantages on high-ranking individuals. In mice, individual position in hierarchies may emerge situationally from current group compositions, or, alternatively, may remain largely stable across groups as an internalized feature. Dominance and subordination are expressed in behaviors like tube competitions or agonistic chasing. The interaction of thes…

Pregnancy leads to many adaptations in the maternal body, most of which are reversible. However, reproductive experience can also result in permanent effects. Here, we investigated how pregnancy influences the somatotrophic system and the lasting effects of reproductive experience on the maternal organism. Reproductive experience induced a pronounced increase in lean body mass and longitudinal gr…

Aggregates of α-synuclein (αS) are hallmarks of synucleinopathies, including Parkinson’s Disease (PD) and Multiple System Atrophy (MSA). We have recently shown that αS lysine acetylation in the soluble monomer pool varies between healthy controls, PD, and MSA patients. We used non-canonical amino acid (ncAA) mutagenesis to express and purify all 12 currently known disease-relevant variants of αS …

Urbanization is a major global driver of biodiversity change, with species responses to urban settings ranging from avoidance to exploitation. To better understand these responses, we conducted a global analysis of urban relative affinity inferred from occurrence data across more than 30,000 animal and plant species. Our synthesis showed a consistent pattern across taxa and biogeographic regions:…

Dendritic spine dysfunction may contribute to the etiology and symptom expression of neuropsychiatric disorders. The intimate relationship between spine morphology and function suggests that decoding disease-related abnormalities from spine morphology can aid in developing synapse-targeted interventions. Here, we describe a population analysis of dendritic spine nanostructure applied to the objec…

Pain perception is strongly influenced by neural states preceding stimulus onset, yet whether such preparatory states can be causally reshaped remains unclear. Using a double-blind design, we tested whether closed-loop neurofeedback can reconfigure preparatory brain dynamics to influence subsequent pain processing. Real, but not sham, feedback enabled learning-dependent enhancement of pre-stimulu…

Plasma membrane glutamate transporters, also known as excitatory amino acid transporters (EAATs), serve to remove glutamate from extracellular spaces following transmitter release. Generally, this process is slow enough that EAAT activity controls the levels of background glutamate rather than the magnitude and time course of synaptic responses. We show here a striking exception to this pattern i…

Humans can readily infer gender from diverse visual categories, including faces, bodies, and objects, yet it remains unclear whether the brain constructs a shared, category-general representation of gender. To fill the gap, we measured neural responses using fMRI while participants viewed female and male stimuli across these three categories. Multivoxel pattern analyses revealed that gender infor…

Active vision requires coordinated attentional processing across both foveal and peripheral receptive fields (RFs), yet the underlying neural dynamics and computational mechanisms remain poorly understood. Previous research has predominantly focused on attention in the visual periphery, leaving the role of foveal processing in naturalistic tasks largely unexplored. Here, we recorded neural activi…