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Dwindling fossil fuels force humanity to search for new energy production routes. Besides energy generation, its storage is a crucial aspect. One promising approach is to store energy from the sun chemically in strained organic molecules, so-called molecular solar thermal (MOST) systems, which can release the stored energy catalytically. A prototypical MOST system is norbornadiene/quadricyclane (NBD/QC) whose energy release and surface chemistry need to be understood. Besides important key parameters such as molecular weight, endergonic reaction profiles, and sufficient quantum yields, the position of the absorption onset of NBD is crucial to cover preferably a large range of sunlight's spectrum. For this purpose, one typically derivatizes NBD with electron-donating and/or electron-accepting substituents. To keep the model system simple enough to be investigated with photoemission techniques, we introduced bromine atoms at the 2,3-position of both compounds. We study the adsorption behavior, energy release, and surface chemistry on Ni(111) using high-resolution X-ray photoelectron spectroscopy (HR-XPS), UV photoelectron spectroscopy, and density functional theory calculations. Both Br2-NBD and Br2-QC partially dissociate on the surface at ∼120 K, with Br2-QC being more stable. Several stable adsorption geometries for intact and dissociated species were calculated, and the most stable structures are determined for both molecules. By temperature-programmed HR-XPS, we were able to observe the conversion of Br2-QC to Br2-NBD in situ at 170 K. The decomposition of Br2-NBD starts at 190 K when C–Br bond cleavage occurs and benzene and methylidene are formed. For Br2-QC, the cleavage already occurs at 130 K when cycloreversion to Br2-NBD sets in. [ABSTRACT FROM AUTHOR]

The scanning differential absorption lidar (DIAL) of the University of Hohenheim (UHOH) is presented. The UHOH DIAL is equipped with an injection-seeded frequency-stabilized high-power Ti:sapphire laser operated at 818 nm with a repetition rate of 250Hz. A scanning transceiver unit with a 80 cm primary mirror receives the atmospheric backscatter signals. The system is capable of water vapor measurements with temporal resolutions of a few seconds and a range resolution between 30 and 300m at daytime. It allows to investigate surface-vegetation-atmosphere exchange processes with high resolution. In this paper, we present the design of the instrument and illustrate its performance with recent water vapor measurements taken in Stuttgart-Hohenheim and in the frame of the HD(CP)² Observational Prototype Experiment (HOPE). HOPE was located near research center Jülich, in western Germany, in spring 2013 as part of the project "High Definition of Clouds and Precipitation for advancing Climate Prediction" (HD(CP)²). Scanning measurements reveal the 3-dimensional structures of the water vapor field. The influence of uncertainties within the calculation of the absorption cross-section at wavelengths around 818 nm for the WV retrieval is discussed. Radiosonde intercomparisons show a very small bias between the instruments of only (-0.04±0.11) gm-3 or (-1.0±2.3)% in the height range of 0.5 to 3 km. [ABSTRACT FROM AUTHOR]

Cells use transient membraneless organelles to regulate biological reaction networks. For example, stress granules selectively store mRNA to downregulate protein expression in response to heat or oxidative stress. Models mimicking this active behavior should be established to better understand in vivo regulation involving compartmentalization. Here we use active, complex coacervate droplets as a model for membraneless organelles to spatiotemporally control the activity of a catalytic DNA (DNAzyme). Upon partitioning into these peptide-RNA droplets, the DNAzyme unfolds and loses its ability to catalyze the cleavage of a nucleic acid strand. We can transiently pause the DNAzyme activity upon inducing droplet formation with fuel. After fuel consumption, the DNAzyme activity autonomously restarts. We envision this system could be used to up and downregulate multiple reactions in a network, helping understand the complexity of a cell's pathways. By creating a network where the DNAzyme could reciprocally regulate the droplet properties, we would have a powerful tool for engineering synthetic cells., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Dynamic combinatorial chemistry (DCC) creates libraries of molecules that are constantly interchanging in a dynamic combinatorial library. When a library member self-assembles, it can displace the equilibria, leading to emergent phenomena like its selection or even its replication. However, such dynamic combinatorial libraries typically operate in or close to equilibrium. This work introduces a new dynamic combinatorial chemistry fueled by a catalytic reaction cycle that forms transient, out-of-equilibrium peptide-based macrocycles. The products in this library exist out of equilibrium at the expense of fuel and are thus regulated by kinetics and thermodynamics. By creating a chemically fueled dynamic combinatorial library with the vast structural space of amino acids, we explored the liquid-liquid phase separation behavior of the library members. The study advances DCCs by showing that peptide structures can be engineered to control the dynamic library's behavior. The work paves the way for creating novel, tunable material systems that exhibit emergent behavior reminiscent of biological systems. These findings have implications for the development of new materials and for understanding life's chemistry., (© 2024 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Genome-wide association studies (GWASs) based on common single nucleotide polymorphisms (SNPs) have identified several loci associated with the risk of monoclonal gammopathy of unknown significance (MGUS), a precursor condition for multiple myeloma (MM). We hypothesized that analyzing haplotypes might be more useful than analyzing individual SNPs, as it could identify functional chromosomal units that collectively contribute to MGUS risk. To test this hypothesis, we used data from our previous GWAS on 992 MGUS cases and 2910 controls from three European populations. We identified 23 haplotypes that were associated with the risk of MGUS at the genome-wide significance level (p < 5 × 10 -8 ) and showed consistent results among all three populations. In 10 genomic regions, strong promoter, enhancer and regulatory element-related histone marks and their connections to target genes as well as genome segmentation data supported the importance of these regions in MGUS susceptibility. Several associated haplotypes affected pathways important for MM cell survival such as ubiquitin-proteasome system (RNF186, OTUD3), PI3K/AKT/mTOR (HINT3), innate immunity (SEC14L1, ZBP1), cell death regulation (BID) and NOTCH signaling (RBPJ). These pathways are important current therapeutic targets for MM, which may highlight the advantage of the haplotype approach homing to functional units., (© 2024. The Author(s).)

Multiple myeloma (MM) is an incurable malignancy of plasma cells. Epidemiological studies indicate a substantial heritable component, but the underlying mechanisms remain unclear. Here, in a genome-wide association study totaling 10,906 cases and 366,221 controls, we identify 35 MM risk loci, 12 of which are novel. Through functional fine-mapping and Mendelian randomization, we uncover two causal mechanisms for inherited MM risk: longer telomeres; and elevated levels of B-cell maturation antigen (BCMA) and interleukin-5 receptor alpha (IL5RA) in plasma. The largest increase in BCMA and IL5RA levels is mediated by the risk variant rs34562254-A at TNFRSF13B. While individuals with loss-of-function variants in TNFRSF13B develop B-cell immunodeficiency, rs34562254-A exerts a gain-of-function effect, increasing MM risk through amplified B-cell responses. Our results represent an analysis of genetic MM predisposition, highlighting causal mechanisms contributing to MM development., (© 2024. The Author(s).)

The ubiquitous RNA chaperone Hfq is involved in the regulation of key biological processes in many species across the bacterial kingdom. In the opportunistic human pathogen Klebsiella pneumoniae , deletion of the hfq gene affects the global transcriptome, virulence, and stress resistance; however, the ligands of the major RNA-binding protein in this species have remained elusive. In this study, we have combined transcriptomic, co-immunoprecipitation, and global RNA interactome analyses to compile an inventory of conserved and species-specific RNAs bound by Hfq and to monitor Hfq-mediated RNA-RNA interactions. In addition to dozens of RNA-RNA pairs, our study revealed an Hfq-dependent small regulatory RNA (sRNA), DinR, which is processed from the 3' terminal portion of dinI mRNA. Transcription of dinI is controlled by the master regulator of the SOS response, LexA. As DinR accumulates in K. pneumoniae in response to DNA damage, the sRNA represses translation of the ftsZ transcript by occupation of the ribosome binding site. Ectopic overexpression of DinR causes depletion of ftsZ mRNA and inhibition of cell division, while deletion of dinR antagonizes cell elongation in the presence of DNA damage. Collectively, our work highlights the important role of RNA-based gene regulation in K. pneumoniae and uncovers the central role of DinR in LexA-controlled division inhibition during the SOS response., Competing Interests: Competing interests statement:The authors declare no competing interest.

Complex coacervation describes the liquid-liquid phase separation of oppositely charged polymers. Active coacervates are droplets in which one of the electrolyte's affinity is regulated by chemical reactions. These droplets are particularly interesting because they are tightly regulated by reaction kinetics. For example, they serve as a model for membraneless organelles that are also often regulated by biochemical transformations such as post-translational modifications. They are also a great protocell model or could be used to synthesize life-they spontaneously emerge in response to reagents, compete, and decay when all nutrients have been consumed. However, the role of the unreactive building blocks, e.g., the polymeric compounds, is poorly understood. Here, we show the important role of the chemically innocent, unreactive polyanion of our chemically fueled coacervation droplets. We show that the polyanion drastically influences the resulting droplets' life cycle without influencing the chemical reaction cycle-either they are very dynamic or have a delayed dissolution. Additionally, we derive a mechanistic understanding of our observations and show how additives and rational polymer design help to create the desired coacervate emulsion life cycles., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Membraneless organelles are droplets in the cytosol that are regulated by chemical reactions. Increasing studies suggest that they are internally organized. However, how these subcompartments are regulated remains elusive. Herein, we describe a complex coacervate-based model composed of two polyanions and a short peptide. With a chemical reaction cycle, we control the affinity of the peptide for the polyelectrolytes leading to distinct regimes inside the phase diagram. We study the transitions from one regime to another and identify new transitions that can only occur under kinetic control. Finally, we show that the chemical reaction cycle controls the liquidity of the droplets offering insights into how active processes inside cells play an important role in tuning the liquid state of membraneless organelles. Our work demonstrates that not only thermodynamic properties but also kinetics should be considered in the organization of multiple phases in droplets., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Active droplets are a great model for membraneless organelles. However, the analysis of these systems remains challenging and is often limited due to the short timescales of their kinetics. We used droplet-based microfluidics to encapsulate a fuel-driven cycle that drives phase separation into coacervate-based droplets to overcome this challenge. This approach enables the analysis of every coacervate-based droplet in the reaction container throughout its lifetime. We discovered that the fuel concentration dictates the formation of the coacervate-based droplets and their properties. We observed that coacervate-based droplets grow through fusion, decay simultaneously independent of their volume, and shrinkage rate scales with their initial volume. This method helps to further understand the regulation of membraneless organelles, and we believe the analysis of individual coacervate-based droplets enables future selection- or evolution-based studies., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Chronic lymphocytic leukemia (CLL) is preceded by monoclonal B-cell lymphocytosis (MBL), a CLL precursor state with a prevalence of up to 12% in aged individuals; however, the duration of MBL and the mechanisms of its evolution to CLL remain largely unknown. In this study, we sequenced the B-cell receptor (BcR) immunoglobulin heavy chain (IGH) gene repertoire of 124 patients with CLL and 118 matched controls in blood samples taken up to 22 years prior to diagnosis. Significant skewing in the BcR IGH gene repertoire was detected in the majority of patients, even before the occurrence of lymphocytosis and irrespective of the clonotypic IGH variable gene somatic hypermutation status. Furthermore, we identified dominant clonotypes belonging to major stereotyped subsets associated with poor prognosis up to 16 years before diagnosis in 14 patients with CLL. In 22 patients with longitudinal samples, the skewing of the BcR IGH gene repertoire increased significantly over time to diagnosis or remained stable at high levels. For 14 of 16 patients with available samples at diagnosis, the CLL clonotype was already present in the prediagnostic samples. Overall, our data indicate that the preclinical phase of CLL could be longer than previously thought, even in adverse-prognostic cases., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

No strong aetiological factors have been established for glioma aside from genetic mutations and variants, ionising radiation and an inverse relationship with asthmas and allergies. Our aim was to investigate the association between pre-diagnostic immune protein levels and glioma risk. We conducted a case-control study nested in the Northern Sweden Health and Disease Study cohort. We analysed 133 glioma cases and 133 control subjects matched by age, sex and date of blood donation. ELISA or Luminex bead-based multiplex assays were used to measure plasma levels of 19 proteins. Conditional logistic regression models were used to estimate the odds ratios and 95% CIs. To further model the protein trajectories over time, the linear mixed-effects models were conducted. We found that the levels of sVEGFR2, sTNFR2, sIL-2Rα and sIL-6R were associated with glioma risk. After adjusting for the time between blood sample collection and glioma diagnosis, the odds ratios were 1.72 (95% CI = 1.01-2.93), 1.48 (95% CI = 1.01-2.16) and 1.90 (95% CI = 1.14-3.17) for sTNFR2, sIL-2Rα and sIL-6R, respectively. The trajectory of sVEGFR2 concentrations over time was different between cases and controls (p-value = 0.031), increasing for cases (0.8% per year) and constant for controls. Our findings suggest these proteins play important roles in gliomagenesis., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Changes in immune marker levels in the blood could be used to improve the early detection of tumor-associated inflammatory processes. To increase predictiveness and utility in cancer detection, intraindividual long-term stability in cancer-free individuals is critical for biomarker candidates as to facilitate the detection of deviation from the norm., Methods: We assessed intraindividual long-term stability for 19 immune markers (IL10, IL13, TNFα, CXCL13, MCP-3, MIP-1α, MIP-1β, fractalkine, VEGF, FGF-2, TGFα, sIL2Rα, sIL6R, sVEGF-R2, sTNF-R1, sTNF-R2, sCD23, sCD27, and sCD30) in 304 cancer-free individuals. Repeated blood samples were collected up to 20 years apart. Intraindividual reproducibility was assessed by calculating intraclass correlation coefficients (ICC) using a linear mixed model., Results: ICCs indicated fair to good reproducibility (ICCs ≥ 0.40 and < 0.75) for 17 of 19 investigated immune markers, including IL10, IL13, TNFα, CXCL13, MCP-3, MIP-1α, MIP-1β, fractalkine, VEGF, FGF-2, TGFα, sIL2Rα, sIL6R, sTNF-R1, sTNF-R2, sCD27, and sCD30. Reproducibility was strong (ICC ≥ 0.75) for sCD23, while reproducibility was poor (ICC < 0.40) for sVEGF-R2. Using a more stringent criterion for reproducibility (ICC ≥ 0.55), we observed either acceptable or better reproducibility for IL10, IL13, CXCL13, MCP-3, MIP-1α, MIP-1β, VEGF, FGF-2, sTNF-R1, sCD23, sCD27, and sCD30., Conclusions: IL10, IL13, CXCL13, MCP-3, MIP-1α, MIP-1β, VEGF, FGF-2, sTNF-R1, sCD23, sCD27, and sCD30 displayed ICCs consistent with intraindividual long-term stability in cancer-free individuals., Impact: Our data support using these markers in prospective longitudinal studies seeking early cancer detection biomarkers., (©2021 American Association for Cancer Research.)

We present detailed studies on the covalent adsorption of molecular oxygen and atomic hydrogen on the hexagonal boron nitride (h-BN) nanomesh on Rh(111). The functionalization of this two-dimensional (2D) material was investigated under ultra-high vacuum conditions using synchrotron radiation-based in situ high-resolution X-ray photoelectron spectroscopy, temperature-programmed X-ray photoelectron spectroscopy and ultraviolet photoelectron spectroscopy. We are able to provide a deep insight into the adsorption behavior and thermal stability of oxygen and hydrogen on h-BN/Rh(111). Oxygen functionalization was achieved via a supersonic molecular beam while hydrogen functionalization was realized using an atomic hydrogen source. Adsorption of the respective species was observed to occur selectively in the pores of h-BN leading to spatially defined modification of the 2D layer. The adsorption of the observed molecular oxygen species was found to be an activated process that requires high-energy oxygen molecules. Upon heating to 700 K, oxygen functionalization was observed to be almost reversible except for small amounts of boron oxides evolving due to the reaction of oxygen with the 2D material. Hydrogen functionalization of h-BN/Rh(111) was fully reversed upon heating to about 640 K., (© 2021 Wiley-VCH GmbH.)

To better understand the role of individual and lifestyle factors in human disease, an exposome-wide association study was performed to investigate within a single-study anthropometry measures and lifestyle factors previously associated with B-cell lymphoma (BCL). Within the European Prospective Investigation into Cancer and nutrition study, 2402 incident BCL cases were diagnosed from 475 426 participants that were followed-up on average 14 years. Standard and penalized Cox regression models as well as principal component analysis (PCA) were used to evaluate 84 exposures in relation to BCL risk. Standard and penalized Cox regression models showed a positive association between anthropometric measures and BCL and multiple myeloma/plasma cell neoplasm (MM). The penalized Cox models additionally showed the association between several exposures from categories of physical activity, smoking status, medical history, socioeconomic position, diet and BCL and/or the subtypes. PCAs confirmed the individual associations but also showed additional observations. The PC5 including anthropometry, was positively associated with BCL, diffuse large B-cell lymphoma (DLBCL) and MM. There was a significant positive association between consumption of sugar and confectionary (PC11) and follicular lymphoma risk, and an inverse association between fish and shellfish and Vitamin D (PC15) and DLBCL risk. The PC1 including features of the Mediterranean diet and diet with lower inflammatory score showed an inverse association with BCL risk, while the PC7, including dairy, was positively associated with BCL and DLBCL risk. Physical activity (PC10) was positively associated with DLBCL risk among women. This study provided informative insights on the etiology of BCL., (© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of Union for International Cancer Control.)

Complex coacervated-based assemblies form when two oppositely charged polyelectrolytes combine to phase separate into a supramolecular architecture. These architectures range from complex coacervate droplets, spherical and worm-like micelles, to vesicles. These assemblies are widely applied, for example, in the food industry, and as underwater or medical adhesives, but they can also serve as a great model for biological assemblies. Indeed, biology relies on complex coacervation to form so-called membraneless organelles, dynamic and transient droplets formed by the coacervation of nucleic acids and proteins. To regulate their function, membraneless organelles are dynamically maintained by chemical reaction cycles, including phosphorylation and dephosphorylation, but exact mechanisms remain elusive. Recently, some model systems also regulated by chemical reaction cycles have been introduced, but how to design such systems and how molecular design affects their properties is unclear. In this work, we test a series of cationic peptides for their chemically fueled coacervation, and we test how their design can affect the dynamics of assembly and disassembly of the emerging structures. We combine them with both homo- and block copolymers and study the morphologies of the assemblies, including morphological transitions that are driven by the chemical reaction cycle. We deduce heuristic design rules that can be applied to other chemically regulated systems. These rules will help develop membraneless organelle model systems and lead to exciting new applications of complex coacervate-based examples like temporary adhesives.

Here, we present a strategy for early molecular marker pattern detection-Subset analysis of Matched Repeated Time points (SMART)-used in a mass-spectrometry-based metabolomics study of repeated blood samples from future glioma patients and their matched controls. The outcome from SMART is a predictive time span when disease-related changes are detectable, defined by time to diagnosis and time between longitudinal sampling, and visualization of molecular marker patterns related to future disease. For glioma, we detect significant changes in metabolite levels as early as eight years before diagnosis, with longitudinal follow up within seven years. Elevated blood plasma levels of myo-inositol, cysteine, N-acetylglucosamine, creatinine, glycine, proline, erythronic-, 4-hydroxyphenylacetic-, uric-, and aceturic acid were particularly evident in glioma cases. We use data simulation to ensure non-random events and a separate data set for biomarker validation. The latent biomarker, consisting of 15 interlinked and significantly altered metabolites, shows a strong correlation to oxidative metabolism, glutathione biosynthesis and monosaccharide metabolism, linked to known early events in tumor development. This study highlights the benefits of progression pattern analysis and provide a tool for the discovery of early markers of disease.

Membraneless organelles like stress granules are active liquid-liquid phase-separated droplets that are involved in many intracellular processes. Their active and dynamic behavior is often regulated by ATP-dependent reactions. However, how exactly membraneless organelles control their dynamic composition remains poorly understood. Herein, we present a model for membraneless organelles based on RNA-containing active coacervate droplets regulated by a fuel-driven reaction cycle. These droplets emerge when fuel is present, but decay without. Moreover, we find these droplets can transiently up-concentrate functional RNA which remains in its active folded state inside the droplets. Finally, we show that in their pathway towards decay, these droplets break apart in multiple droplet fragments. Emergence, decay, rapid exchange of building blocks, and functionality are all hallmarks of membrane-less organelles, and we believe that our work could be powerful as a model to study such organelles.

We present simulations suggesting that it is possible to minimize the systematic errors of differential absorption lidar (DIAL) measurements caused by the Rayleigh-Doppler effect by selecting an online frequency close to one of the inflection points on either side of the absorption line. Thus, it seems advantageous to select an absorption line of suitable cross section at these points on the line slopes rather than at the peak. First, we extend the classical simulation study of Ansmann (1985) for another water vapor absorption line but again with the online frequency at the line peak. As expected, we also found large systematic errors of more than 40% at the edges of aerosol layers and clouds. Second, we simulate the systematic errors for other online frequencies away from the peak for the same input profile. The results demonstrate that the errors vanish close to the inflection points. Since both the shape of the absorption lines and the width of the broadened backscatter signal depend on the atmospheric conditions, these optimum frequencies vary slightly with height and climatology. Third, we calculate the errors for a typical aerosol profile of the planetary boundary layer obtained from lidar measurements. With this case, we discuss how to select practically the online frequency so that the errors are minimized for all heights of interest. We found that the error reduces from 20 to < 1% at the top of the planetary boundary layer while, at the same time, the error reduces from 6 to 2% in 5 km.