Local Coordination Environment of Lanthanides Adsorbed onto Cr- and Zr-based Metal-Organic Frameworks.

Separating individual lanthanide (Ln) elements in aqueous mixtures is challenging. Ion-selective capture by porous materials, such as metal-organic frameworks (MOFs), is a promising approach. To design ion-selective MOFs, molecular details of the Ln adsorption complexes within the MOFs must be understood. We determine the local coordination environment of lanthanides Nd(III), Gd(III), and Lu(III) adsorbed onto Cr(III)-based terephthalate MOF (Cr-MIL-101) and Zr(IV)-based Universitet in Oslo MOFs (UiO-66 and UiO-68) and their derivatives. In the Cr(III)- and Zr(IV)-based MOFs, Ln adsorb as inner-sphere complexes at the metal oxo clusters, regardless of whether the organic linkers are decorated with amino groups. Missing linkers result in favorable Ln binding sites at oxo clusters; however, Ln can coordinate to metal sites even with linkers in place. MOF functionalization with phosphonate groups led to Ln chemisorption onto these groups, which out-compete metal cluster sites. Ln form monodentate and bidentate and mononuclear and binuclear surface complexes. We conclude that MOFs for ion-selective Ln capture can be designed by a combination of (1) maximizing metal-lanthanide interactions via shared O atoms at the metal oxo cluster sites, where mixed oxo clusters can lead to ion-selective Ln adsorption, and (2) functionalizing MOFs with Ln-selective groups capable of out-completing the metal oxo cluster sites.

The epidermal circadian clock integrates and subverts brain signals to guarantee skin homeostasis.

In mammals, the circadian clock network drives daily rhythms of tissue-specific homeostasis. To dissect daily inter-tissue communication, we constructed a mouse minimal clock network comprising only two nodes: the peripheral epidermal clock and the central brain clock. By transcriptomic and functional characterization of this isolated connection, we identified a gatekeeping function of the peripheral tissue clock with respect to systemic inputs. The epidermal clock concurrently integrates and subverts brain signals to ensure timely execution of epidermal daily physiology. Timely cell-cycle termination in the epidermal stem cell compartment depends upon incorporation of clock-driven signals originating from the brain. In contrast, the epidermal clock corrects or outcompetes potentially disruptive feeding-related signals to ensure the optimal timing of DNA replication. Together, we present an approach for cataloging the systemic dependencies of daily temporal organization in a tissue and identify an essential gate-keeping function of peripheral circadian clocks that guarantees tissue homeostasis.

Brain-muscle communication prevents muscle aging by maintaining daily physiology.

A molecular clock network is crucial for daily physiology and maintaining organismal health. We examined the interactions and importance of intratissue clock networks in muscle tissue maintenance. In arrhythmic mice showing premature aging, we created a basic clock module involving a central and a peripheral (muscle) clock. Reconstituting the brain-muscle clock network is sufficient to preserve fundamental daily homeostatic functions and prevent premature muscle aging. However, achieving whole muscle physiology requires contributions from other peripheral clocks. Mechanistically, the muscle peripheral clock acts as a gatekeeper, selectively suppressing detrimental signals from the central clock while integrating important muscle homeostatic functions. Our research reveals the interplay between the central and peripheral clocks in daily muscle function and underscores the impact of eating patterns on these interactions.

Disproportionation chemistry in K2PtCl4 visualized at atomic resolution using scanning transmission electron microscopy.

The direct observation of a solid-state chemical reaction can reveal otherwise hidden mechanisms that control the reaction kinetics. However, probing the chemical bond breaking and formation at the molecular level remains challenging because of the insufficient spatial-temporal resolution and composition analysis of available characterization methods. Using atomic-resolution differential phase-contrast imaging in scanning transmission electron microscopy, we have visualized the decomposition chemistry of K2PtCl4 to identify its transient intermediate phases and their interfaces that characterize the chemical reduction process. The crystalline structure of K2PtCl4 is found to undergo a disproportionation reaction to form K2PtCl6, followed by gradual reduction to crystalline Pt metal and KCl. By directly imaging different Pt─Cl bond configurations and comparing them to models predicted via density functional theory calculations, a causal connection between the initial and final states of a chemical reaction is established, showcasing new opportunities to resolve reaction pathways through atomistic experimental visualization.

Impact of Bmal1 Rescue and Time-Restricted Feeding on Liver and Muscle Proteomes During the Active Phase in Mice.

Molecular clocks and daily feeding cycles support metabolism in peripheral tissues. Although the roles of local clocks and feeding are well defined at the transcriptional level, their impact on governing protein abundance in peripheral tissues is unclear. Here, we determine the relative contributions of local molecular clocks and daily feeding cycles on liver and muscle proteomes during the active phase in mice. LC-MS/MS was performed on liver and gastrocnemius muscle harvested 4 h into the dark phase from WT, Bmal1 KO, and dual liver- and muscle-Bmal1-rescued mice under either ad libitum feeding or time-restricted feeding during the dark phase. Feeding-fasting cycles had only minimal effects on levels of liver proteins and few, if any, on the muscle proteome. In contrast, Bmal1 KO altered the abundance of 674 proteins in liver and 80 proteins in muscle. Local rescue of liver and muscle Bmal1 restored ∼50% of proteins in liver and ∼25% in muscle. These included proteins involved in fatty acid oxidation in liver and carbohydrate metabolism in muscle. For liver, proteins involved in de novo lipogenesis were largely dependent on Bmal1 function in other tissues (i.e., the wider clock system). Proteins regulated by BMAL1 in liver and muscle were enriched for secreted proteins. We found that the abundance of fibroblast growth factor 1, a liver secreted protein, requires BMAL1 and that autocrine fibroblast growth factor 1 signaling modulates mitochondrial respiration in hepatocytes. In liver and muscle, BMAL1 is a more potent regulator of dark phase proteomes than daily feeding cycles, highlighting the need to assess protein levels in addition to mRNA when investigating clock mechanisms. The proteome is more extensively regulated by BMAL1 in liver than in muscle, and many metabolic pathways in peripheral tissues are reliant on the function of the clock system as a whole.

Quantifying Atomically Dispersed Catalysts Using Deep Learning Assisted Microscopy.

The catalytic performance of atomically dispersed catalysts (ADCs) is greatly influenced by their atomic configurations, such as atom-atom distances, clustering of atoms into dimers and trimers, and their distributions. Scanning transmission electron microscopy (STEM) is a powerful technique for imaging ADCs at the atomic scale; however, most STEM analyses of ADCs thus far have relied on human labeling, making it difficult to analyze large data sets. Here, we introduce a convolutional neural network (CNN)-based algorithm capable of quantifying the spatial arrangement of different adatom configurations. The algorithm was tested on different ADCs with varying support crystallinity and homogeneity. Results show that our algorithm can accurately identify atom positions and effectively analyze large data sets. This work provides a robust method to overcome a major bottleneck in STEM analysis for ADC catalyst research. We highlight the potential of this method to serve as an on-the-fly analysis tool for catalysts in future in situ microscopy experiments.

Ion solvation as a predictor of lanthanide adsorption structures and energetics in alumina nanopores.

Adsorption reactions at solid-water interfaces define elemental fate and transport and enable contaminant clean-up, water purification, and chemical separations. For nanoparticles and nanopores, nanoconfinement may lead to unexpected and hard-to-predict products and energetics of adsorption, compared to analogous unconfined surfaces. Here we use X-ray absorption fine structure spectroscopy and operando flow microcalorimetry to determine nanoconfinement effects on the energetics and local coordination environment of trivalent lanthanides adsorbed on Al2O3 surfaces. We show that the nanoconfinement effects on adsorption become more pronounced as the hydration free energy, ΔGhydr, of a lanthanide decreases. Neodymium (Nd3+) has the least exothermic ΔGhydr (-3336 kJ·mol-1) and forms mostly outer-sphere complexes on unconfined Al2O3 surfaces but shifts to inner-sphere complexes within the 4 nm Al2O3 pores. Lutetium (Lu3+) has the most exothermic ΔGhydr (-3589 kJ·mol-1) and forms inner-sphere adsorption complexes regardless of whether Al2O3 surfaces are nanoconfined. Importantly, the energetics of adsorption is exothermic in nanopores only, and becomes endothermic with increasing surface coverage. Changes to the energetics and products of adsorption in nanopores are ion-specific, even within chemically similar trivalent lanthanide series, and can be predicted by considering the hydration energies of adsorbing ions.

Circadian transcriptome processing and analysis: a workflow for muscle stem cells.

Circadian rhythms coordinate biological processes with Earth's 24-h daily light/dark cycle. In the last years, efforts in the field of chronobiology have sought to understand the ways in which the circadian clock controls transcription across tissues and cells. This has been supported by the development of different bioinformatic approaches that allow the identification of 24-h oscillating transcripts. This workflow aims to describe how to isolate muscle stem cells for RNA sequencing analysis from a typical circadian experiment and introduces bioinformatic tools suitable for the analysis of circadian transcriptomes.

Liver and muscle circadian clocks cooperate to support glucose tolerance in mice.

Physiology is regulated by interconnected cell and tissue circadian clocks. Disruption of the rhythms generated by the concerted activity of these clocks is associated with metabolic disease. Here we tested the interactions between clocks in two critical components of organismal metabolism, liver and skeletal muscle, by rescuing clock function either in each organ separately or in both organs simultaneously in otherwise clock-less mice. Experiments showed that individual clocks are partially sufficient for tissue glucose metabolism, yet the connections between both tissue clocks coupled to daily feeding rhythms support systemic glucose tolerance. This synergy relies in part on local transcriptional control of the glucose machinery, feeding-responsive signals such as insulin, and metabolic cycles that connect the muscle and liver. We posit that spatiotemporal mechanisms of muscle and liver play an essential role in the maintenance of systemic glucose homeostasis and that disrupting this diurnal coordination can contribute to metabolic disease.

The central clock suffices to drive the majority of circulatory metabolic rhythms.

Life on Earth anticipates recurring 24-hour environmental cycles via genetically encoded molecular clocks active in all mammalian organs. Communication between these clocks controls circadian homeostasis. Intertissue communication is mediated, in part, by temporal coordination of metabolism. Here, we characterize the extent to which clocks in different organs control systemic metabolic rhythms, an area that remains largely unexplored. We analyzed the metabolome of serum from mice with tissue-specific expression of the clock gene Bmal1. Having functional hepatic and muscle clocks can only drive a minority (13%) of systemic metabolic rhythms. Conversely, limiting Bmal1 expression to the central pacemaker in the brain restores rhythms to 57% of circulatory metabolites. Rhythmic feeding imposed on clockless mice resulted in a similar rescue, indicating that the central clock mainly regulates metabolic rhythms via behavior. These findings explicate the circadian communication between tissues and highlight the importance of the central clock in governing those signals.