Thyroid hormone remodels cortex to coordinate body-wide metabolism and exploration.

Animals adapt to environmental conditions by modifying the function of their internal organs, including the brain. To be adaptive, alterations in behavior must be coordinated with the functional state of organs throughout the body. Here, we find that thyroid hormone-a regulator of metabolism in many peripheral organs-directly activates cell-type-specific transcriptional programs in the frontal cortex of adult male mice. These programs are enriched for axon-guidance genes in glutamatergic projection neurons, synaptic regulatory genes in both astrocytes and neurons, and pro-myelination factors in oligodendrocytes, suggesting widespread plasticity of cortical circuits. Indeed, whole-cell electrophysiology revealed that thyroid hormone alters excitatory and inhibitory synaptic transmission, an effect that requires thyroid hormone-induced gene regulatory programs in presynaptic neurons. Furthermore, thyroid hormone action in the frontal cortex regulates innate exploratory behaviors and causally promotes exploratory decision-making. Thus, thyroid hormone acts directly on the cerebral cortex in males to coordinate exploratory behaviors with whole-body metabolic state.

Hindbrain modules differentially transform activity of single collicular neurons to coordinate movements.

Seemingly simple behaviors such as swatting a mosquito or glancing at a signpost involve the precise coordination of multiple body parts. Neural control of coordinated movements is widely thought to entail transforming a desired overall displacement into displacements for each body part. Here we reveal a different logic implemented in the mouse gaze system. Stimulating superior colliculus (SC) elicits head movements with stereotyped displacements but eye movements with stereotyped endpoints. This is achieved by individual SC neurons whose branched axons innervate modules in medulla and pons that drive head movements with stereotyped displacements and eye movements with stereotyped endpoints, respectively. Thus, single neurons specify a mixture of endpoints and displacements for different body parts, not overall displacement, with displacements for different body parts computed at distinct anatomical stages. Our study establishes an approach for unraveling motor hierarchies and identifies a logic for coordinating movements and the resulting pose.

Pervasive, Coordinated Protein-Level Changes Driven by Transcript Isoform Switching during Meiosis.

To better understand the gene regulatory mechanisms that program developmental processes, we carried out simultaneous genome-wide measurements of mRNA, translation, and protein through meiotic differentiation in budding yeast. Surprisingly, we observed that the levels of several hundred mRNAs are anti-correlated with their corresponding protein products. We show that rather than arising from canonical forms of gene regulatory control, the regulation of at least 380 such cases, or over 8% of all measured genes, involves temporally regulated switching between production of a canonical, translatable transcript and a 5' extended isoform that is not efficiently translated into protein. By this pervasive mechanism for the modulation of protein levels through a natural developmental program, a single transcription factor can coordinately activate and repress protein synthesis for distinct sets of genes. The distinction is not based on whether or not an mRNA is induced but rather on the type of transcript produced.

Eukaryotic DNA Replication Fork.

This review focuses on the biogenesis and composition of the eukaryotic DNA replication fork, with an emphasis on the enzymes that synthesize DNA and repair discontinuities on the lagging strand of the replication fork. Physical and genetic methodologies aimed at understanding these processes are discussed. The preponderance of evidence supports a model in which DNA polymerase ε (Pol ε) carries out the bulk of leading strand DNA synthesis at an undisturbed replication fork. DNA polymerases α and δ carry out the initiation of Okazaki fragment synthesis and its elongation and maturation, respectively. This review also discusses alternative proposals, including cellular processes during which alternative forks may be utilized, and new biochemical studies with purified proteins that are aimed at reconstituting leading and lagging strand DNA synthesis separately and as an integrated replication fork.

Independent and Stochastic Action of DNA Polymerases in the Replisome.

It has been assumed that DNA synthesis by the leading- and lagging-strand polymerases in the replisome must be coordinated to avoid the formation of significant gaps in the nascent strands. Using real-time single-molecule analysis, we establish that leading- and lagging-strand DNA polymerases function independently within a single replisome. Although average rates of DNA synthesis on leading and lagging strands are similar, individual trajectories of both DNA polymerases display stochastically switchable rates of synthesis interspersed with distinct pauses. DNA unwinding by the replicative helicase may continue during such pauses, but a self-governing mechanism, where helicase speed is reduced by ∼80%, permits recoupling of polymerase to helicase. These features imply a more dynamic, kinetically discontinuous replication process, wherein contacts within the replisome are continually broken and reformed. We conclude that the stochastic behavior of replisome components ensures complete DNA duplication without requiring coordination of leading- and lagging-strand synthesis. PAPERCLIP.

Splicing Kinetics and Coordination Revealed by Direct Nascent RNA Sequencing through Nanopores.

Understanding how splicing events are coordinated across numerous introns in metazoan RNA transcripts requires quantitative analyses of transient RNA processing events in living cells. We developed nanopore analysis of co-transcriptional processing (nano-COP), in which nascent RNAs are directly sequenced through nanopores, exposing the dynamics and patterns of RNA splicing without biases introduced by amplification. Long nano-COP reads reveal that, in human and Drosophila cells, splicing occurs after RNA polymerase II transcribes several kilobases of pre-mRNA, suggesting that metazoan splicing transpires distally from the transcription machinery. Inhibition of the branch-site recognition complex SF3B rapidly diminished global co-transcriptional splicing. We found that splicing order does not strictly follow the order of transcription and is associated with cis-acting elements, alternative splicing, and RNA-binding factors. Further, neighboring introns in human cells tend to be spliced concurrently, implying that splicing of these introns occurs cooperatively. Thus, nano-COP unveils the organizational complexity of RNA processing.

Acetylation coordinates the crosstalk between carbon metabolism and ammonium assimilation in Salmonella enterica.

Enteric bacteria use up to 15% of their cellular energy for ammonium assimilation via glutamine synthetase (GS)/glutamate synthase (GOGAT) and glutamate dehydrogenase (GDH) in response to varying ammonium availability. However, the sensory mechanisms for effective and appropriate coordination between carbon metabolism and ammonium assimilation have not been fully elucidated. Here, we report that in Salmonella enterica, carbon metabolism coordinates the activities of GS/GDH via functionally reversible protein lysine acetylation. Glucose promotes Pat acetyltransferase-mediated acetylation and activation of adenylylated GS. Simultaneously, glucose induces GDH acetylation to inactivate the enzyme by impeding its catalytic centre, which is reversed upon GDH deacetylation by deacetylase CobB. Molecular dynamics (MD) simulations indicate that adenylylation is required for acetylation-dependent activation of GS. We show that acetylation and deacetylation occur within minutes of "glucose shock" to promptly adapt to ammonium/carbon variation and finely balance glutamine/glutamate synthesis. Finally, in a mouse infection model, reduced S. enterica growth caused by the expression of adenylylation-mimetic GS is rescued by acetylation-mimicking mutations. Thus, glucose-driven acetylation integrates signals from ammonium assimilation and carbon metabolism to fine-tune bacterial growth control.

Accelerated hermaphrodite maturation on male pheromones suggests a general principle of coordination between larval behavior and development.

Environment in general and social signals in particular could alter development. In Caenorhabditis elegans, male pheromones hasten development of hermaphrodite larvae. We show that this involves acceleration of growth and both somatic and germline development during the last larval stage (L4). Larvae exposed to male pheromones spend more time in L3 and less in the quiescent period between L3 and L4. This behavioral alteration improves provision in early L4, likely allowing for faster development. Larvae must be exposed to male pheromones in late L3 for behavioral and developmental effects to occur. Latter portions of other larval stages also contain periods of heightened sensitivity to environmental signals. Behavior during the early part of the larval stages is biased toward exploration, whereas later the emphasis shifts to food consumption. We argue that this organization allows assessment of the environment to identify the most suitable patch of resources, followed by acquisition of sufficient nutrition and salient information for the developmental events in the next larval stage. Evidence from other species indicates that such coordination of behavior and development may be a general feature of larval development.

Homophily, selection, and choice in segregation models.

Schelling's 1971 work on the dynamics of segregation showed that even a small degree of homophily, the desire to live among like neighbors, can lead to a starkly segregated population. One of the driving factors for this result is that the notion of homophily used is based on group identities that are exogenous and immutable. In contrast, we consider a homophily that arises from the desire to be with neighbors who are behaviorally similar, not necessarily those who have the same group identity. The distinction matters because behaviors are neither exogenous nor immutable but choices that can change as individuals adapt to their neighborhoods. We show that in such an environment, integration rather than segregation is the typical outcome. However, the tendency toward adaptation and integration can be impeded when economic frictions in the form of income inequality and housing cost are present.

Cellular and molecular organization of the Drosophila foregut.

The animal foregut is the first tissue to encounter ingested food, bacteria, and viruses. We characterized the adult Drosophila foregut using transcriptomics to better understand how it triages consumed items for digestion or immune response and manages resources. Cell types were assigned and validated using GFP-tagged and Gal4 reporter lines. Foregut-associated neuroendocrine cells play a major integrative role by coordinating gut activity with nutrition, the microbiome, and circadian cycles; some express clock genes. Multiple epithelial cell types comprise the proventriculus, the central foregut organ that secretes the peritrophic matrix (PM) lining the gut. Analyzing cell types synthesizing individual PM layers revealed abundant mucin production close to enterocytes, similar to the mammalian intestinal mucosa. The esophagus and salivary gland express secreted proteins likely to line the esophageal surface, some of which may generate a foregut commensal niche housing specific gut microbiome species. Overall, our results imply that the foregut coordinates dietary sensing, hormonal regulation, and immunity in a manner that has been conserved during animal evolution.

Phosphorescent metallaknots of Au(I)-bis(acetylide) strands directed by Cu(I) π-coordination.

Knots containing metal atoms as part of their continuous strand backbone are termed as metallaknots. While several metallaknots have been synthesized through one-pot self-assembly, the designed synthesis of metallaknots by controlling the arrangement of entanglements and strands connectivity remains unexplored. Here, we report the synthesis of metallaknots composed with Au(I)-bis(acetylide) linkages and templated by Cu(I) ions. Varying the ratio of the building blocks results in the switchable formation of two trefoil knots with different stoichiometries and symmetries (C2 or D3) and an entangled metalla-complex. While the entangled complex formed serendipitously, the strand ends can be subsequently linked through coordinative closure to generate a 41 metallaknot in a highly designable fashion. The comparable structural characteristics of resulting metalla-complexes allow us to probe the correlations between their topologies and photophysical properties, showing the backbone rigidity of knots endows complexes with excellent phosphorescent properties. This strategy, in conjunction with the coordinative closure approach, provides a straightforward route for the formation of highly phosphorescent metallaknots that were previously challenging to access.

Pink noise promotes sooner state transitions during bimanual coordination.

The seemingly straightforward task of tying one's shoes requires a sophisticated interplay of joints, muscles, and neural pathways, posing a formidable challenge for researchers studying the intricacies of coordination. A widely accepted framework for measuring coordinated behavior is the Haken-Kelso-Bunz (HKB) model. However, a significant limitation of this model is its lack of accounting for the diverse variability structures inherent in the coordinated systems it frequently models. Variability is a pervasive phenomenon across various biological and physical systems, and it changes in healthy adults, older adults, and pathological populations. Here, we show, both empirically and with simulations, that manipulating the variability in coordinated movements significantly impacts the ability to change coordination patterns-a fundamental feature of the HKB model. Our results demonstrate that synchronized bimanual coordination, mirroring a state of healthy variability, instigates earlier transitions of coordinated movements compared to other variability conditions. This suggests a heightened adaptability when movements possess a healthy variability. We anticipate our study to show the necessity of adapting the HKB model to encompass variability, particularly in predictive applications such as neuroimaging, cognition, skill development, biomechanics, and beyond.

Extinct and extant termites reveal the fidelity of behavior fossilization in amber.

Fossils encompassing multiple individuals provide rare direct evidence of behavioral interactions among extinct organisms. However, the fossilization process can alter the spatial relationship between individuals and hinder behavioral reconstruction. Here, we report a Baltic amber inclusion preserving a female-male pair of the extinct termite species Electrotermes affinis. The head-to-abdomen contact in the fossilized pair resembles the tandem courtship behavior of extant termites, although their parallel body alignment differs from the linear alignment typical of tandem runs. To solve this inconsistency, we simulated the first stage of amber formation, the immobilization of captured organisms, by exposing living termite tandems to sticky surfaces. We found that the posture of the fossilized pair matches trapped tandems and differs from untrapped tandems. Thus, the fossilized pair likely is a tandem running pair, representing the direct evidence of the mating behavior of extinct termites. Furthermore, by comparing the postures of partners on a sticky surface and in the amber inclusion, we estimated that the male likely performed the leader role in the fossilized tandem. Our results demonstrate that past behavioral interactions can be reconstructed despite the spatial distortion of body poses during fossilization. Our taphonomic approach demonstrates how certain behaviors can be inferred from fossil occurrences.

Supramolecular coordination platinum metallacycle-based multilevel wound dressing for bacteria sensing and wound healing.

The exploitation of novel wound healing methods with real-time infection sensing and high spatiotemporal precision is highly important for human health. Pt-based metal-organic cycles/cages (MOCs) have been employed as multifunctional antibacterial agents due to their superior Pt-related therapeutic efficiency, various functional subunits and specific geometries. However, how to rationally apply these nanoscale MOCs on the macroscale with controllable therapeutic output is still challenging. Here, a centimeter-scale Pt MOC film was constructed via multistage assembly and subsequently coated on a N,N'-dimethylated dipyridinium thiazolo[5,4-d]thiazole (MPT)-stained silk fabric to form a smart wound dressing for bacterial sensing and wound healing. The MPT on silk fabric could be used to monitor wound infection in real-time through the bacteria-mediated reduction of MPT to its radical form via a color change. The MPT radical also exhibited an excellent photothermal effect under 660 nm light irradiation, which could not only be applied for photothermal therapy but also induce the disassembly of the Pt MOC film suprastructure. The highly ordered Pt MOC film suprastructure exhibited high biosafety, while it also showed improved antibacterial efficiency after thermally induced disassembly. In vitro and in vivo studies revealed that the combination of the Pt MOC film and MPT-stained silk can provide real-time information on wound infection for timely treatment through noninvasive techniques. This study paves the way for bacterial sensing and wound healing with centimeter-scale metal-organic materials.

Regulation of anion-Na+ coordination chemistry in electrolyte solvates for low-temperature sodium-ion batteries.

High-performance sodium storage at low temperature is urgent with the increasingly stringent demand for energy storage systems. However, the aggravated capacity loss is induced by the sluggish interfacial kinetics, which originates from the interfacial Na+ desolvation. Herein, all-fluorinated anions with ultrahigh electron donicity, trifluoroacetate (TFA-), are introduced into the diglyme (G2)-based electrolyte for the anion-reinforced solvates in a wide temperature range. The unique solvation structure with TFA- anions and decreased G2 molecules occupying the inner sheath accelerates desolvation of Na+ to exhibit decreased desolvation energy from 4.16 to 3.49 kJ mol-1 and 24.74 to 16.55 kJ mol-1 beyond and below -20 °C, respectively, compared with that in 1.0 M NaPF6-G2. These enable the cell of Na||Na3V2(PO4)3 to deliver 60.2% of its room-temperature capacity and high capacity retention of 99.2% after 100 cycles at -40 °C. This work highlights regulation of solvation chemistry for highly stable sodium-ion batteries at low temperature.

Precise coordination of high-loading Fe single atoms with sulfur boosts selective generation of nonradicals.

Nonradicals are effective in selectively degrading electron-rich organic contaminants, which unfortunately suffer from unsatisfactory yield and uncontrollable composition due to the competitive generation of radicals. Herein, we precisely construct a local microenvironment of the carbon nitride-supported high-loading (~9 wt.%) Fe single-atom catalyst (Fe SAC) with sulfur via a facile supermolecular self-assembly strategy. Short-distance S coordination boosts the peroxymonosulfate (PMS) activation and selectively generates high-valent iron-oxo species (FeIV=O) along with singlet oxygen (1O2), significantly increasing the 1O2 yield, PMS utilization, and p-chlorophenol reactivity by 6.0, 3.0, and 8.4 times, respectively. The composition of nonradicals is controllable by simply changing the S content. In contrast, long-distance S coordination generates both radicals and nonradicals, and could not promote reactivity. Experimental and theoretical analyses suggest that the short-distance S upshifts the d-band center of the Fe atom, i.e., being close to the Fermi level, which changes the binding mode between the Fe atom and O site of PMS to selectively generate 1O2 and FeIV=O with a high yield. The short-distance S-coordinated Fe SAC exhibits excellent application potential in various water matrices. These findings can guide the rational design of robust SACs toward a selective and controllable generation of nonradicals with high yield and PMS utilization.

Coordination dynamics between fuel cell and battery technologies in the transition to clean cars.

Significant progress reconciling economic activities with a stable climate requires radical and rapid technological change in multiple sectors. Here, we study the case of the automotive industry's transition to electric vehicles, which involved choosing between two different technologies: fuel cell electric vehicles (FCEVs) or battery electric vehicles (BEVs). We know very little about the role that such technological uncertainty plays in shaping the strategies of firms, the efficacy of technological and climate policies, and the speed of technological transitions. Here, we explain that the choice between these two technologies posed a global and multisectoral coordination game, due to technological complementarities and the global organization of the industry's markets and supply chains. We use data on patents, supply-chain relationships, and national policies to document historical trends and industry dynamics for these two technologies. While the industry initially focused on FCEVs, around 2008, the technological paradigm shifted to BEVs. National-level policies had a limited ability to coordinate global players around a type of clean car technology. Instead, exogenous innovation spillovers from outside the automotive sector played a critical role in solving this coordination game in favor of BEVs. Our results suggest that global and cross-sectoral technology policies may be needed to accelerate low-carbon technological change in other sectors, such as shipping or aviation. This enriches the existing theoretical paradigm, which ignores the scale of interdependencies between technologies and firms.

Coordination engineering for iron-based hexacyanoferrate as a high-stability cathode for sodium-ion batteries.

Iron-based hexacyanoferrate (Fe-HCF) are promising cathode materials for sodium-ion batteries (SIBs) due to their unique open-channel structure that facilitates fast ion transport and framework stability. However, practical implementation of SIBs has been hindered by low initial Coulombic efficiency (ICE), poor rate performance, and short lifespan. Herein, we report a coordination engineering to synthesize sodium-rich Fe-HCF as cathodes for SIBs through a uniquely designed 10-kg-scale chemical reactor. Our study systematically investigated the relationship between coordination surroundings and the electrochemical behavior. Building on this understanding, the cathode delivered a reversible capacity of 99.3 mAh g-1 at 5 C (1 C = 100 mA g-1), exceptional rate capability (51 mAh g-1 even at 100 C), long lifespan (over 15,000 times at 50 C), and a high ICE of 92.7%. A full cell comprising the Fe-HCF cathode and hard carbon (HC) anode exhibited an impressive cyclic stability with a high-capacity retention rate of 98.3% over 1,000 cycles. Meanwhile, this material can be readily scaled to the practical levels of yield. The findings underscore the potential of Fe-HCF as cathodes for SIBs and highlight the significance of controlling nucleation and morphology through coordination engineering for a sustainable energy storage system.

Boosted hydrogen evolution kinetics of heteroatom-doped carbons with isolated Zn as an accelerant.

Carbon-based single-atom catalysts, a promising candidate in electrocatalysis, offer insights into electron-donating effects of metal center on adjacent atoms. Herein, we present a practical strategy to rationally design a model catalyst with a single zinc (Zn) atom coordinated with nitrogen and sulfur atoms in a multilevel carbon matrix. The Zn site exhibits an atomic interface configuration of ZnN4S1, where Zn's electron injection effect enables thermal-neutral hydrogen adsorption on neighboring atoms, pushing the activity boundaries of carbon electrocatalysts toward electrochemical hydrogen evolution to an unprecedented level. Experimental and theoretical analyses confirm the low-barrier Volmer-Tafel mechanism of proton reduction, while the multishell hollow structures facilitate the hydrogen evolution even at high current intensities. This work provides insights for understanding the actual active species during hydrogen evolution reaction and paves the way for designing high-performance electrocatalysts.

Enriching surface-ordered defects on WO3 for photocatalytic CO2-to-CH4 conversion by water.

Defect engineering has been widely applied in semiconductors to improve photocatalytic properties by altering the surface structures. This study is about the transformation of inactive WO3 nanosheets to a highly effective CO2-to-CH4 conversion photocatalyst by introducing surface-ordered defects in abundance. The nonstoichiometric WO3-x samples were examined by using aberration-corrected electron microscopy. Results unveil abundant surface-ordered terminations derived from the periodic {013} stacking faults with a defect density of 20.2%. The {002} surface-ordered line defects are the active sites for fixation CO2, transforming the inactive WO3 nanosheets into a highly active catalyst (CH4: O2 = 8.2: 16.7 µmol h-1). We believe that the formation of the W-O-C-W-O species is a critical step in the catalytic pathways. This work provides an atomic-level comprehension of the structural defects of catalysts for activating small molecules.