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Exercise intensity and training alter the innate immune cell type and chromosomal origins of circulating cell-free DNA in humans

Exercising regularly promotes health, but these benefits are complicated by acute inflammation induced by exercise. A potential source of inflammation is cell-free DNA (cfDNA), yet the cellular origins, molecular causes, and immune system interactions of exercise-induced cfDNA are unclear. To study these, 10 healthy individuals were randomized to a 12-wk exercise program of either high-intensity tactical training (HITT) or traditional moderate-intensity training (TRAD). Blood plasma was collected pre- and postexercise at weeks 0 and 12 and after 4 wk of detraining upon program completion. Whole-genome enzymatic methylation sequencing (EM-seq) with cell-type proportion deconvolution was applied to cfDNA obtained from the 50 plasma samples and paired to concentration measurements for 90 circulating cytokines. Acute exercise increased the release of cfDNA from neutrophils, dendritic cells (DCs), and macrophages proportional to exercise intensity. Exercise training reduced cfDNA released in HITT participants but not TRAD and from DCs and macrophages but not neutrophils. For most participants, training lowered mitochondrial cfDNA at rest, even after detraining. Using a sequencing analysis approach we developed, we concluded that rapid ETosis, a process of cell death where cells release DNA extracellular traps, was the likely source of cfDNA, demonstrated by enrichment of nuclear DNA. Further, several cytokines were induced by acute exercise, such as IL-6, IL-10, and IL-16, and training attenuated the induction of only IL-6 and IL-17F. Cytokine levels were not associated with cfDNA induction, suggesting that these cytokines are not the main cause of exercise-induced cfDNA. Overall, exercise intensity and training modulated cfDNA release and cytokine responses, contributing to the anti-inflammatory effects of regular exercise.

Universality in diffusion-controlled nucleation and growth

Nucleation and growth are studied in a system that undergoes diffusion-controlled condensation under gradual changes in parameters, such as cooling. It is demonstrated that when the Gibbs–Thompson effect becomes negligible, the system falls into a universal regime. i.e., the final droplet size distribution remains invariant under certain rescaling of system parameters. An approximate yet very accurate analytic form is obtained for the final droplet size distribution in this regime.

Codon bias, nucleotide selection, and genome size predict in situ bacterial growth rate and transcription in rewetted soil

In soils, the first rain after a prolonged dry period represents a major pulse event impacting soil microbial community function, yet we lack a full understanding of the genomic traits associated with the microbial response to rewetting. Genomic traits such as codon usage bias and genome size have been linked to bacterial growth in soils—however, often through measurements in culture. Here, we used metagenome-assembled genomes (MAGs) with 18 O-water stable isotope probing and metatranscriptomics to track genomic traits associated with growth and transcription of soil microorganisms over one week following rewetting of a grassland soil. We found that codon bias in ribosomal protein genes was the strongest predictor of growth rate. We also found higher growth rates in bacteria with smaller genomes, suggesting that reduced genome size enables a faster response to pulses in soil bacteria. Faster transcriptional upregulation of ribosomal protein genes was associated with high codon bias and increased nucleotide skew. We found that several of these relationships existed within phyla, indicating that these associations between genomic traits and activity could be generalized characteristics of soil bacteria. Finally, we used publicly available metagenomes to assess the distribution of codon bias across a pH gradient and found that microbial communities in higher pH soils—which are often more water limited and pulse driven—have higher codon usage bias in their ribosomal protein genes. Together, these results provide evidence that genomic characteristics affect soil microbial activity during rewetting and pose a potential fitness advantage for soil bacteria where water and nutrient availability are episodic.

Corresponding-states framework for classical and quantum fluids—Beyond Feynman–Hibbs

Effective potential methods, obtained by applying a quantum correction to a classical pair potential, are widely used for describing the thermophysical properties of fluids with mild nuclear quantum effects. In case of strong nuclear quantum effects, such as for liquid hydrogen and helium, the accuracy of these quantum corrections deteriorates significantly, but at present no simple alternatives are available. In this work, we solve this issue by developing a new, three-parameter corresponding-states principle that remains applicable in the regions of the phase diagram where quantum effects become significant. The new principle emerges from a mapping procedure, which shows that quantum-corrected pair potentials can be made conformal to their underlying classical pair potential by modifying the latter’s repulsive range. This mapping enables an accurate description of fluids with quantum-corrected interactions based on off-the-shelf methods for classical fluids (e.g., equations of state, classical density functional theory, and entropy scaling) using effective, mapped intermolecular-potential parameters. These effective parameters depend on temperature and molecular mass; simple analytic equations in case of a classical Mie potential with Feynman–Hibbs quantum corrections are presented. Using Mie Feynman–Hibbs force fields from the literature, we show that this procedure provides accurate predictions for the properties of fluids with mild nuclear quantum effects, such as neon or hydrogen at moderate temperatures. Moreover, by adjusting the functional form of the effective intermolecular-potential parameters to experimental data for helium and hydrogen, we are able to apply the corresponding-states principle for optimal quantum-corrected pair potentials that far surpass the accuracy of the Feynman–Hibbs correction.

The androgen clock is an epigenetic predictor of long-term male hormone exposure

Aging is a complex process characterized by biological decline and a wide range of molecular alterations to cells, including changes to DNA methylation. In this study, we used a male-specific epigenetic marker of aging to build an epigenetic predictor that measures long-term androgen exposure in sheep and mice (median absolute error of 4.3 and 1.4 mo, respectively). We term this predictor the androgen clock and show its “tick” is mediated by the androgen receptor and can be accelerated beyond that in normal male mice by supplementing females with dihydrotestosterone. Conversely, the removal of androgens by castration in sheep completely halted the androgen clock. In addition to potential applications in medicine and agriculture, we predict the androgen clock will prove a useful model to understand the mechanisms and processes of age-associated DNA methylation change because it can be precisely enhanced and halted using small molecule manipulation with few additional effects on the cell.

Cavity correlations and the onset of charge ordering at charged interfaces: A modified Poisson–Fermi approach

Charge layering in the close vicinity of charged interfaces is a well-known effect, extensively reported in both experiments and simulations of Room Temperature Ionic Liquids (RTILs) and concentrated electrolytes. The traditional Poisson–Fermi (PF) theory is able to successfully describe overcrowding effects but fails to reproduce charge ordering even in strong coupling regimes. Simple models, yet capable of investigating the interplay between these important interfacial phenomena, are still lacking. In order to bridge this gap, we herein present a modified PF approach that is able to capture layering effects in strong coupling regimes typical of RTIL. The modification is based on the introduction of charge cavities around test-particles, which simply extend the exclusion volume effects to also incorporate the accompanying depletion of charges due to particle insertion. The addition of this simple ingredient is shown to reproduce overscreening and charge ordering, thereby extending the predictive power of the PF approach to strong coupling regimes. Using a linear response theory, we were able to study the emergence of charge ordering based on two characteristic lengths: a wavelength responsible for charge layering, along with a damping length that screens charge oscillations. At large ionic strengths and strong couplings, the system undergoes a transition to undamped charge layering. The transition takes place when the poles of the Fourier components of the linear potential become real-valued. This criterion allows one to identify the transition line across the parameter space, thus delimiting the region of stability against unscreened charge ordering.

Polarization resolved second harmonic scattering of neat water in the right angle and forward scattering geometries

Liquid water still remains an ubiquitous liquid whose molecular organization requires careful investigation. In this work, we present a study of the second harmonic scattering (SHS) intensity for two different scattering angles, namely, the forward and the right angle geometries. This method performed at optical wavelengths is indeed selective toward long correlation lengths. A polarization analysis demonstrates that it is then possible to clearly evidence a coherent component to the total SHS intensity using a fast Fourier transform analysis of the SHS intensity as a function of the fundamental angle of polarization despite its weak relative contribution. A model is then derived based on the rotational invariants to fully unravel the different contributions to the SHS intensity for the two right angle and forward angles of scattering as well as the dependence with the fundamental beam polarization angle. This model fully supports the experimental results, further confirming an azimuthal geometry of the water–water orientational correlation function in neat water.

Shifting equilibria in a warming boreal forest

2D Raman-THz spectroscopy of imidazolium-based ionic liquids

An investigation of the low-frequency (i.e., less than 5 THz), inter-molecular dynamics of three imidazolium-based ionic liquids—1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([C4mim][NTf2]), 1-butyl-3-methylimidazolium dicyanamide ([C4mim][DCA]), and 1-ethyl-3-methylimidazolium dicyanamide ([C2mim][DCA])—is presented using two-dimensional (2D) Raman-THz spectroscopy combined with molecular dynamics (MD) simulations. By observing an echo in the 2D Raman-THz response, the experimental results indicate that the substitution of a small [DCA]− anion with a larger [NTf2]− one leads to a substantial increase in the structural inhomogeneity of the low-frequency modes of the system. These findings are corroborated by MD simulations, comparing the experimentally observed echo decay times to those of a computed velocity echo. The comparison suggests that the echo decay time reflects the instantaneous amount of structural order related to the charge alternation network, which is enhanced for the ionic liquid with the larger anion.

State shifts in the deep Critical Zone drive landscape evolution in volcanic terrains

Volcanic provinces are among the most active but least well understood landscapes on Earth. Here, we show that the central Cascade arc, USA, exhibits systematic spatial covariation of topography and hydrology that are linked to aging volcanic bedrock, suggesting systematic controls on landscape evolution. At the Cascade crest, a locus of Quaternary volcanism, water circulates deeply through the upper ∼ 1 km of crust but transitions to shallow and dominantly horizontal flow as rocks age away from the arc front. We argue that this spatial pattern reflects a temporal state shift in the deep Critical Zone. Chemical weathering at depth, surface particulate deposition, and tectonic forcing drive landscapes away from an initial state with minimal topographic dissection, large vertical hydraulic conductivity, abundant lakes, and muted hydrographs toward a state of deep fluvial dissection, small vertical hydraulic conductivity, few lakes, and flashy hydrographs. This state shift has major implications for regional water resources. Drill hole temperature profiles imply at least 81 km 3 of active groundwater currently stored at the Cascade Range crest, with discharge variability a strong function of bedrock age. Deeply circulating groundwater also impacts volcanism, and Holocene High Cascades eruptions reflect explosive magma–water interactions that increase regional volcanic hazard potential. We propose that a Critical Zone state shift drives volcanic landscape evolution in wet climates and represents a framework for understanding interconnected solid earth dynamics and climate in these terrains.

Nanoscale water behavior and its impact on adsorption: A case study with CNTs and diclofenac

Water is a fundamental component of life, playing a critical role in regulating metabolic processes and facilitating the dissolution and transport of essential molecules. However, emerging contaminants, such as pharmaceuticals, pose significant challenges to water quality and safety. Nanomaterial-based technologies emerge as a promising solution for removing those contaminants from water. Nevertheless, interfacial water plays a major role in the adsorption of chemical compounds in nanomaterials—as it plays in biological processes such as protein folding, enzyme activity, and drug delivery. To understand this role, in this study, we employ molecular dynamics simulations to explore the adsorption dynamics of potassium diclofenac on single-walled carbon nanotubes (SWCNTs) and double-walled carbon nanotubes (DWCNTs), considering both dry and wet conditions. Our findings reveal that the structuring of water molecules around CNTs creates hydration layers that significantly influence the accessibility of active sites and the interaction strength between contaminants and adsorbents. Our analysis indicates higher energy barriers for adsorption in DWCNTs compared to SWCNTs, which is attributed to stronger water–surface interactions. This research highlights the importance of understanding nanoscale water behavior for optimizing the design and functionality of nanomaterials for water purification. These findings can guide the development of more efficient and selective nanomaterials, enhancing contaminant removal and ensuring safer water resources while contributing to a deeper understanding of fundamental biological interactions.

Visual pigments underlie the sensitivity difference between day and night vision

Enhancing the accuracy of XPS calculations: Exploring hybrid basis set schemes for CVS-EOMIP-CCSD calculations

Reliable computational methodologies and basis sets for modeling x-ray spectra are essential for extracting and interpreting electronic and structural information from experimental x-ray spectra. In particular, the trade-off between numerical accuracy and computational cost due to the size of the basis set is a major challenge, since molecular orbitals undergo extreme relaxation in the core-hole state. To gain clarity on the changes in electronic structure induced by the formation of a core-hole, the use of sufficiently flexible basis for expanding the orbitals, particularly for the core region, has been shown to be essential. This work focuses on the refinement of core-hole ionized state calculations using the equation-of-motion coupled cluster family of methods through an extensive analysis on the effectiveness of “hybrid” and mixed basis sets. In this investigation, we utilize the CVS-EOMIP-CCSD method in combination and construct hybrid basis sets piecewise from readily available Dunning’s correlation consistent basis sets in order to calculate x-ray ionization energies (IEs) for a set of small gas phase molecules. Our results provide insights into the impact of basis sets on the CVS-EOMIP-CCSD calculations of K-edge IEs of first-row p-block elements. These insights enable us to understand more about the basis set dependence of the core IEs computed and allow us to establish a protocol for deriving reliable and cost-effective theoretical estimates for computing IEs of small molecules containing such elements.

Resolving electrochemically triggered topological defect dynamics and structural degradation in layered oxides

Understanding topological defects-controlled structural degradation of layered oxides—a key cathode material for high-performance lithium-ion batteries—plays a critical role in developing next-generation cathode materials. Here, by constructing a nanobattery in an electron microscope enabling atomic-scale monitoring of electrochemcial reactions, we captured the electrochemically driven atomistic dynamics and evolution of dislocations—a most important topological defect in material. We deciphered how dislocations nucleate, move, and annihilate within layered cathodes at the atomic scale. Specifically, we found two types of dislocation configurations, i.e., single dislocations and dislocation dipoles. Both pure dislocation glide/climb and mixed motions were captured, and the dislocation glide and climb velocities were first experimentally measured. Moreover, dislocation activity-mediated structural degradation such as crack nucleation, phase transformation, and lattice reorientation was unraveled. Our work provides deep insights into the atomistic dynamics of electrochemically driven dislocation activities in layered oxides.

Structural determinants of oxygen resistance and Zn ²⁺ -mediated stability of the [FeFe]-hydrogenase from <i>Clostridium beijerinckii</i>

[FeFe]-hydrogenases catalyze the reversible two-electron reduction of two protons to molecular hydrogen. Although these enzymes are among the most efficient H 2 -converting biocatalysts in nature, their catalytic cofactor (termed H-cluster) is irreversibly destroyed upon contact with dioxygen. The [FeFe]-hydrogenase CbA5H from Clostridium beijerinckii has a unique mechanism to protect the H-cluster from oxygen-induced degradation. The protective strategy of CbA5H was proposed based on a partial protein structure of CbA5H’s oxygen-shielded form. Here, we present a cryo-EM structure of 2.2 Å resolution from the entire enzyme in its dimeric and active state and elucidate the structural parameters of the reversible cofactor protection mechanism. We found that both subunits of the homodimeric structure of CbA5H have a Zn 2+ -binding four-helix domain, which does not play a role in electron transport as described for other complex protein structures. Biochemical data instead confirm that two [4Fe-4S] clusters are responsible for electron transfer in CbA5H, while the identified zinc atom is critical for oligomerization and protein stability.

Correction for Tveit et al., Widespread soil bacterium that oxidizes atmospheric methane

Burrow collapse is not the only explanation for rapid, noncatastrophic preservation of 3D dinosaurs

Correction for van de Water et al., Therapeutic stem cells expressing variants of EGFR-specific nanobodies have antitumor effects

Reply to Emery-Wetherell: Taphonomy of Lujiatun 3D dinosaurs is inconsistent with death and burial by lahars

Streptokinase is dispensable in Streptococcus dysgalactiae subspecies equisimilis infections of human dendritic cells

Abstract In recent years, increased numbers of severe Streptococcus dysgalactiae subsp. equisimilis (SDSE) infections, including necrotizing soft tissue infections (NSTIs), have been reported. One of the main virulence factors of SDSE is streptokinase (Ska). Ska promotes bacterial spread in the tissue through Ska-plasminogen interactions and subsequent activation of plasminogen to plasmin. In this study, the impact of streptokinase on SDSE infections of human monocyte-derived dendritic cells (moDCs) was investigated. MoDCs were infected with SDSE strain S118 and its isogenic mutant lacking streptokinase. All infections were performed with and without human serum to compare direct Ska-mediated as well as plasmin activity-related effects. Intracellular killing kinetics, moDC viability and maturation, as well as the release of pro-inflammatory cytokines were assessed. Irrespective of the strain and experimental conditions, the bacteria were equally phagocytosed and killed. MoDCs remained viable, readily matured and secreted equal amounts of cytokines in response to S118 as well as S118Δska infections. Our data demonstrate that moDCs response to SDSE infections is not affected by Ska or its respective plasminogen activating function.