Prokaryotic nanocompartments form synthetic organelles in a eukaryote

Compartmentalization of proteins into organelles is a promising strategy for enhancing the productivity of engineered eukaryotic organisms. However, approaches that co-opt endogenous organelles may be limited by the potential for unwanted crosstalk and disruption of native metabolic functions. Here, we present the construction of synthetic non-endogenous organelles in the eukaryotic yeast Saccharomyces cerevisiae, based on the prokaryotic family of self-assembling proteins known as encapsulins. We establish that encapsulins self-assemble to form nanoscale compartments in yeast, and that heterologous proteins can be selectively targeted for compartmentalization. Housing destabilized proteins within encapsulin compartments afford protection against proteolytic degradation in vivo, while the interaction between split protein components is enhanced upon co-localization within the compartment interior. Furthermore, encapsulin compartments can support enzymatic catalysis, with substrate turnover observed for an encapsulated yeast enzyme. Encapsulin compartments therefore represent a modular platform, orthogonal to existing organelles, for programming synthetic compartmentalization in eukaryotes

An X-ray spectroscopy study of structural stability of superhydrogenated pyrene derivatives

The stability of polycyclic aromatic hydrocarbons (PAHs) upon soft X-ray absorption is of crucial relevance for PAH survival in X-ray dominated regions (XDRs). PAH stability depends on molecular size but also on the degree of hydrogenation that is related to H2 formation in the interstellar medium (ISM). In this project, we intend to reveal the changes of electronic structure caused by hydrogenation and the impact of hydrogenation on the stability of the carbon backbone for cationic pyrene and its hydrogenated derivatives by analysis of near C K-edge soft X-ray photoions. In our experiments, the PAH cations were trapped in a cryogenic radiofrequency (RF) linear ion trap and exposed to monochromatic X-rays with energies from 279 eV to 300 eV. The photo-products were mass-analyzed by means of time-of-flight (TOF) spectroscopy. Partial ion yields (PIYs) were then studied as a function of photon energy. X-ray absorption spectra computed by time-dependent density functional theory (TD-DFT) aided the interpretation of the experimental results. A very good agreement between experimental data and TDDFT with short-range corrected (SRC) functionals for all PAH ions was reached. The near-edge X-ray absorption mass spectra (NEXAMS) exhibit clear peaks due to C 1s transitions to singly occupied molecular orbitals SOMO and to low-lying unoccupied molecular orbitals. In contrast to coronene cations, where hydrogen attachment drastically increases photostability of coronene, the influence of hydrogenation on photostability is substantially weaker for pyrene cations. Here, hydrogen attachment even destabilizes the molecular structure. An astrophysical model describes the half-life of PAH ions in interstellar environments

Exposing the Oxygen-Centered Radical Character of the Tetraoxido Ruthenium(VIII) Cation [RuO4]+

The tetraoxido ruthenium(VIII) radical cation, [RuO4]+, should be a strong oxidizing agent, but has been difficult to produce and investigate so far. In our X-ray absorption spectroscopy study, in combination with quantum-chemical calculations, we show that [RuO4]+, produced via oxidation of ruthenium cations by ozone in the gas phase, forms the oxygen-centered radical ground state. The oxygen-centered radical character of [RuO4]+ is identified by the chemical shift at the ruthenium M3 edge, indicative of ruthenium(VIII), and by the presence of a characteristic low-energy transition at the oxygen K edge, involving an oxygen-centered singly-occupied molecular orbital, which is suppressed when the oxygen-centered radical is quenched by hydrogenation of [RuO4]+ to the closed-shell [RuO4H]+ ion. Hydrogen-atom abstraction from methane is calculated to be only slightly less exothermic for [RuO4]+ than for [OsO4]+

The Highest Oxidation State of Rhodium: Rhodium(VII) in [RhO3]+

Although the highest possible oxidation states of all transition elements are rare, they are not only of fundamental interest but also relevant as potentially strong oxidizing agents. In general, the highest oxidation states are found in the electron‐rich late transition elements of groups 7–9 of the periodic table. Rhodium is the first element of the 4d transition metal series for which the highest known oxidation state does not equal its group number of 9, but reaches only a significantly lower value of +6 in exceptional cases. Higher oxidation states of rhodium have remained elusive so far. In a combined mass spectrometry, X‐ray absorption spectroscopy, and quantum‐chemical study of gas‐phaseRhOn+ (n=1–4), we identify RhO3+ as the 1A1' trioxidorhodium(VII) cation, the first chemical species to contain rhodium in the +7 oxidation state, which is the third‐highest oxidation state experimentally verified among all elements in the periodic table

A comparative laboratory study of soft X-ray-induced ionization and fragmentation of five small PAH cations

The interaction between polycyclic aromatic hydrocarbon (PAH) radical cations and X-rays predominantly leads to photofragmentation, a process that strongly depends on PAH size and geometry. In our experiments, five prototypical PAHs were exposed to monochromatic soft X-ray photons with energies in the C K-edge regime. As a function of soft X-ray photon energy, photoion yields were obtained by means of time-of-flight mass spectrometry. The resulting near-edge X-ray absorption mass spectra were interpreted using time-dependent density functional theory (TD-DFT) with a short-range corrected functional. We found that the carbon backbone of anthracene$$^+$$(C$$_{14}$$H$$_{10}^+$$), pyrene$$^+$$(C$$_{16}$$H$$_{10}^+$$) and coronene$$^+$$(C$$_{24}$$H$$_{12}^+$$) can survive soft X-ray absorption, even though mostly intermediate size fragments are formed. In contrast, for hexahydropyrene$$^+$$(C$$_{16}$$H$$_{16}^+$$) and triphenylene$$^+$$(C$$_{18}$$H$$_{12}^+$$) molecular survival is not observed and the fragmentation pattern is dominated by small fragments. For a given excitation energy, molecular survival evidently does not simply correlate with PAH size but strongly depends on other PAH properties

Factors associated with cognitive decline and delirium after transcatheter aortic valve implantation: Preliminary evidence

Background: Transcatheter aortic valve implantation (TAVI) has become the standard for treating severe symptomatic aortic stenosis in those with prohibitive surgical risk. Cognitive complications, including delirium and cognitive decline are common following TAVI, yet an understanding of pre-procedural factors associated with these outcomes is lacking. This prospective observational study set out to identify geriatric pre-procedural factors associated with post-procedural delirium and cognitive decline in patients undergoing TAVI. / Methods: Cognitive outcomes of TAVI patients aged ≥60 years (N=32) were measured over one-year post-TAVI. Pre-procedural measures included frailty, gait, visual symptoms, voice pitch, dysphagia, blink rate, mood, and sleep. Primary outcomes were post-procedural delirium and cognitive decline. / Results: Delirium was present in 25% of patients over two days following TAVI and 26% experienced cognitive decline in the year post-TAVI. Daily physical activity was a protective factor against cognitive decline, and worse baseline visual memory was associated with delirium. While non-significant and with very large confidence intervals, moderate to large effect sizes were found for associations between slowed gait speed, pre-existing atrial fibrillation, and dysphagia for delirium, and slower gait speed, higher blink rate, pre-existing atrial fibrillation for cognitive decline. / Conclusion: Though underpowered, measures of considerable effect size were identified (although non-significant and with large variability). In larger studies, these novel geriatric factors could further be explored for predicting cognitive complications following TAVI. Improvement of risk prediction for cognitive decline and delirium following TAVI could assist with early identification of those at risk, informing clinical decision-making and allowing for targeted intervention to reduce post-procedural incidence of these complications

Magnetic nanodoping: Atomic control of spin states in cobalt doped silver clusters

The interaction of magnetic dopants with delocalized electron states can result in interesting many-body physics. Here, the magnetic properties of neutral and charged finite silver metal host clusters with a magnetic cobalt atom impurity were investigated experimentally by exploiting the complementary methods of Stern- Gerlach molecular beam deflection and x-ray magnetic circular dichroism spectroscopy and are accompanied by density functional theory calculations and charge transfer multiplet simulations. The influence of the number of valence electrons and the consequences of impurity encapsulation were addressed in free size-selected, singly cobalt-doped silver clusters CoAg0,n+ (n = 2–15). Encapsulation of the dopant facilitates the formation of delocalized electronic shells with complete hybridization of the impurity 3d- and the host 5s-derived orbitals, which results in impurity valence electron delocalization, effective spin relaxation, and a low-spin ground state. In the exohedral size regime, spin pairing in the free electron gas formed by the silver 5s electrons is the dominating driving force determining the local 3d occupation of the impurity and therefore, adjusting the spin magnetic moment accordingly

Cystatin C is associated with adverse COVID-19 outcomes in diverse populations

COVID-19 has highly variable clinical courses. The search for prognostic host factors for COVID-19 outcome is a priority. We performed logistic regression for ICU admission against a polygenic score (PGS) for Cystatin C (CyC) production in patients with COVID-19. We analyzed the predictive value of longitudinal plasma CyC levels in an independent cohort of patients hospitalized with COVID-19. In four cohorts spanning European and African ancestry populations, we identified a significant association between CyC-production PGS and odds of critical illness (n cases=2,319), with the strongest association captured in the UKB cohort (OR 2.13, 95% CI 1.58-2.87, p=7.12e-7). Plasma proteomics from an independent cohort of hospitalized COVID-19 patients ( n cases = 131) demonstrated that CyC production was associated with COVID-specific mortality (p=0.0007). Our findings suggest that CyC may be useful for stratification of patients and it has functional role in the host response to COVID-19.Peer reviewe