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Unlocking single-atom induced electronic metal-support interactions in electrocatalytic one-electron water oxidation for wastewater purification
Proteome-wide determinants of co-translational chaperone binding in bacteria
Abstract Chaperones are essential to the co-translational folding of most proteins. However, the principles of co-translational chaperone interaction throughout the proteome are poorly understood, as current methods are restricted to few substrates and cannot capture nascent protein folding or chaperone binding sites, precluding a comprehensive understanding of productive and erroneous protein biosynthesis. Here, by integrating genome-wide selective ribosome profiling, single-molecule tools, and computational predictions using AlphaFold we show that the binding of the main E. coli chaperones involved in co-translational folding, Trigger Factor (TF) and DnaK correlates with “unsatisfied residues” exposed on nascent partial folds – residues that have begun to form tertiary structure but cannot yet form all native contacts due to ongoing translation. This general principle allows us to predict their co-translational binding across the proteome based on sequence only, which we verify experimentally. The results show that TF and DnaK stably bind partially folded rather than unfolded conformers. They also indicate a synergistic action of TF guiding intra-domain folding and DnaK preventing premature inter-domain contacts, and reveal robustness in the larger chaperone network (TF, DnaK, GroEL). Given the complexity of translation, folding, and chaperone functions, our predictions based on general chaperone binding rules indicate an unexpected underlying simplicity.
Universal vibrational anharmonicity in carbyne-like materials
Abstract Carbyne, an infinite linear chain of carbon atoms, is the truly one-dimensional allotrope of carbon. While ideal carbyne and its fundamental properties have remained elusive, carbyne-like materials such as carbyne chains confined inside carbon nanotubes are available for study. Here, we probe the longitudinal optical phonon (C mode) of confined carbyne chains by Raman spectroscopy up to the third overtone. We observe a strong vibrational anharmonicity that increases with decreasing C mode frequency, reaching up to 8% for the third overtone. Moreover, we find that the relation between vibrational anharmonicity and C mode frequency is universal to carbyne-like materials, including ideal carbyne. This establishes experimentally that carbyne and related materials have pronounced anharmonic potential landscapes which must be included in the theoretical description of their structure and properties.
A general assay platform to study protein pharmacology using ligand-dependent structural dynamics
Abstract Drug design strategies represent a fundamental challenge in chemical biology that could benefit from the development of next-generation high-throughput assays. Here we demonstrate that structural dynamic changes induced by ligand binding can be transmitted to a sensor protein fused to a target protein terminus. Here, NanoLuc luciferase, used as the intact protein or its α-complementation peptide, was fused to seven proteins from distinct enzyme superfamilies resulting in sensitive ligand-dependent bioluminescent outputs. This finding allows a general non-competitive, function-independent, quantitative, isothermal gain-of-signal ligand binding readout. As applied to chemical library high throughput screening, we can observe multivariate pharmacologic outputs including cofactor-induced synergy in ligand binding, as well as an example of allosteric site binding. The structural dynamics response assay format described here can enable the investigation of proteins precluded from study due to cost-prohibitive, insensitive, or technically challenging assays, including from cell lysates containing endogenously expressed gene edited proteins.
Endothelial major vault protein alleviates vascular remodeling via promoting Parkin-mediated mitophagy
BiDAC-dependent degradation of plasma membrane proteins by the endolysosomal system
Mapping pesticide-induced metabolic alterations in human gut bacteria
Publisher Correction: Trends in global and regional incidence and prevalence of hypertensive disorders in pregnancy (1990–2021): an age-period-cohort analysis
Prevalence and impact of ECMO cannula colonization: a single center study
Abstract During ECMO therapy, infections are common and have substantial impact on treatment outcomes. However, data on the prevalence and clinical impact of microbial ECMO cannula colonization are scarce. Between October 2020 and May 2022, we evaluated 112 ECMO cannulas from 58 patients for microbial colonization using sonication fluid culture & 16S-rRNA-PCR (n = 105), or roll plate method (n = 7). 38 (33.9%) cannulas from 30 (51.7%) patients showed evidence for bacterial colonization with the predominance of coagulase-negative staphylococci (67.4%). Antipseudomonal β-Lactam treatment at cannulation and ECMO initiation at referring hospitals were associated with cannula colonization upon multivariable per-patient analysis. The prevalence of bloodstream infections was equally low and the occurrence of fever after and number of anti-infective drugs given during ECMO therapy was similar in patients with and without exposure to colonized cannulas. Finally, there was no association of cannula colonization with adverse outcomes. In summary, our data suggest that bacterial ECMO cannula colonization does not affect the clinical course of patients and thus discourage routine microbial assessment of cannula tips or even cannula exchange in the absence of clinical signs of cannula infection.
Life cycle assessment of glass fibre versus flax fibre reinforced composite ship hulls
Factors influencing the anxiety and depression status in patients undergoing in vitro fertilization-embryo transfer assisted pregnancy
Children’s attribution of mental states to humans and social robots assessed with the Theory of Mind Scale
Life satisfaction of adopted and non-adopted adolescents in four European countries
Somatosensory and prefrontal cortex activity relates to emotional outcomes and hair cortisol concentration in chronic postsurgical pain
Combined treatment with mesenchymal stem cells and therapeutic hypothermia for neonatal hypoxic ischemic encephalopathy: a phase 1/2 randomized trial
Abstract Neonatal hypoxic ischemic encephalopathy (nHIE) is a serious disease that causes severe and chronic neurological damage. Hypothermia therapy improves patients’ outcomes albeit with some limitations, but combining it with treatment with cord blood cells (analogous to mesenchymal stem cells [MSCs]) reportedly improves its effectiveness. TEMCELL HS Inj. (Temcell), a human bone marrow-derived MSC product used for acute graft-versus-host disease, seems an appropriate candidate for this combination therapy. Therefore, we performed a randomized, parallel-group study to compare combined treatment with Temcell and hypothermia versus hypothermia therapy-alone to evaluate the safety and efficacy of Temcell in nHIE patients. The primary endpoint was treatment response defined as an overall developmental quotient of ≥ 85 at 18 months of age. Fourteen patients were enrolled and randomized, with 7 assigned to each group. Both groups had similar demographic characteristics and nHIE severity. Treatment response was observed in 4 of the 6 (66.7%) patients in the Temcell combination group, and in 4 of the 7 patients (57.1%) in the hypothermia therapy-alone group. No marked differences in safety profile were observed between the groups. These results indicate that the efficacy of Temcell combined with hypothermia is comparable to therapeutic hypothermia for patients with nHIE. Clinical Trial Registration: jRCT1080224818.