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The aggregation of α-synuclein (αS) plays a key role in Parkinson's disease (PD) etiology. While the onset of PD is age-related, the cellular quality control system appears to regulate αS aggregation throughout most human life. Intriguingly, the protein 14-3-3τ has been demonstrated to delay αS aggregation and the onset of PD in various models. However, the molecular mechanisms behind this delay remain elusive. Our study confirms the delay in αS aggregation by 14-3-3τ, unveiling a concentration-dependent relation. Utilizing microscale thermophoresis (MST) and single-molecule burst analysis, we quantified the early αS multimers and concluded that these multimers exhibit properties that classify them as nanoscale condensates that form in a cooperative process, preceding the critical nucleus for fibril formation. Significantly, the αS multimer formation mechanism changes dramatically in the presence of scaffold protein 14-3-3τ. Our data modeling suggests that 14-3-3τ modulates the multimerization process, leading to the creation of mixed multimers or co-condensates, comprising both αS and 14-3-3τ. These mixed multimers form in a noncooperative process. They are smaller, more numerous, and distinctively not on the pathway to amyloid formation. Importantly, 14-3-3τ thus acts in the very early stage of αS multimerization, ensuring that αS does not aggregate but remains soluble and functional. This offers long-sought novel entries for the pharmacological modulation of PD.

Sodium hypochlorite (NaClO) is widely used for the chemical cleaning of fouled ultrafiltration (UF) membranes. Various studies performed on polymeric membranes demonstrate that long-term (>100 h) exposure to NaClO deteriorates the physicochemical properties of the membranes, leading to reduced performance and service life. However, the effect of NaClO cleaning on ceramic membranes, particularly the number of cleaning cycles they can undergo to alleviate irreversible fouling, remains poorly understood. Silicon carbide (SiC) membranes have garnered widespread attention for water and wastewater treatment, but their chemical stability in NaClO has not been studied. Low-pressure chemical vapor deposition (LP-CVD) provides a simple and economical route to prepare/modify ceramic membranes. As such, LP-CVD facilitates the preparation of SiC membranes: (a) in a single step; and (b) at much lower temperatures (700-900 °C) in comparison with sol-gel methods (ca. 2000 °C). In this work, SiC ultrafiltration (UF) membranes were prepared via LP-CVD at two different deposition temperatures and pressures. Subsequently, their chemical stability in NaClO was investigated over 200 h of aging. Afterward, the properties and performance of as-prepared SiC UF membranes were evaluated before and after aging to determine the optimal deposition conditions. Our results indicate that the SiC UF membrane prepared via LP-CVD at 860 °C and 100 mTorr exhibited excellent resistance to NaClO aging, while the membrane prepared at 750 °C and 600 mTorr significantly deteriorated. These findings not only highlight a novel preparation route for SiC membranes in a single step via LP-CVD, but also provide new insights about the careful selection of LP-CVD conditions for SiC membranes to ensure their long-term performance and robustness under harsh chemical cleaning conditions.

The presence of deposits of alpha-synuclein (αS) fibrils in the cells of the brain is a hallmark of several α-synucleinopathies, including Parkinson's disease. As most disease cases are not familial, it is likely that external factors play a role in the disease onset. One of the external factors that may influence the disease onset is viral infection. It has recently been shown in in vitro assays that in the presence of SARS-Cov-2 N-protein, αS fibril formation is faster and proceeds in an unusual two-step aggregation process. Here, we show that faster fibril formation is not due to the SARS-CoV-2 N-protein-catalysed formation of an aggregation-prone nucleus. Instead, aggregation starts with the formation of a population of mixed αS/N-protein fibrils with low affinity for αS. Mixed amyloid fibrils, composed of two different proteins, have not been observed before. After the depletion of N-protein, fibril formation comes to a halt, until a slow transformation into fibrils with characteristics of a pure αS fibril strain occurs. This transformation into a strain of αS fibrils subsequently results in a second phase of fibril growth until a new equilibrium is reached. We hypothesize that this fibril strain transformation may be of relevance in the cell-to-cell spread of the αS pathology and disease onset.

Theoretical concepts from polymer physics are often used to describe intrinsically disordered proteins (IDPs). However, amino acid interactions within and between regions of the protein can lead to deviations from typical polymer scaling behavior and even to short-lived secondary structures. To investigate the key interactions in the dynamic IDP α-synuclein (αS) at the amino acid level, we conducted single-molecule fluorescence resonance energy transfer (smFRET) experiments and coarse-grained molecular dynamics (CG-MD) simulations. We find excellent agreement between experiments and simulations. Our results show that a physiological salt solution is a good solvent for αS and that the protein is highly dynamic throughout its entire chain, with local intra- and inter-regional interactions leading to deviations from global scaling. Specifically, we observe expansion in the C-terminal region, compaction in the NAC region, and a slightly smaller distance between the C- and N-termini than expected. Our simulations indicate that the compaction in the NAC region results from hydrophobic aliphatic contacts, mostly between valine and alanine residues, and cation-π interactions between lysine and tyrosine. In addition, hydrogen bonds also seem to contribute to the compaction of the NAC region. The expansion of the C-terminal region is due to intraregional electrostatic repulsion and increased chain stiffness from several prolines. Overall, our study demonstrates the effectiveness of combining smFRET experiments with CG-MD simulations to investigate the key interactions in highly dynamic IDPs at the amino acid level.

Haemodialysis is life sustaining but expensive, provides limited removal of uraemic solutes, is associated with poor patient quality of life and has a large carbon footprint. Innovative dialysis technologies such as portable, wearable and implantable artificial kidney systems are being developed with the aim of addressing these issues and improving patient care. An important challenge for these technologies is the need for continuous regeneration of a small volume of dialysate. Dialysate recycling systems based on sorbents have great potential for such regeneration. Novel dialysis membranes composed of polymeric or inorganic materials are being developed to improve the removal of a broad range of uraemic toxins, with low levels of membrane fouling compared with currently available synthetic membranes. To achieve more complete therapy and provide important biological functions, these novel membranes could be combined with bioartificial kidneys, which consist of artificial membranes combined with kidney cells. Implementation of these systems will require robust cell sourcing; cell culture facilities annexed to dialysis centres; large-scale, low-cost production; and quality control measures. These challenges are not trivial, and global initiatives involving all relevant stakeholders, including academics, industrialists, medical professionals and patients with kidney disease, are required to achieve important technological breakthroughs., (© 2023. Springer Nature Limited.)

Two-dimensional transition metal dichalcogenide (TMDC) materials have shown great potential for usage in opto-electronic devices, especially down to the regime of a few layers to a single layer. However, at these limits, the material properties can be strongly influenced by the interfaces. By using photoconductive atomic force microscopy, we show a local enhancement of photoconductivity at the nanoscale in bilayer molybdenum disulfide on mica, where water is confined between the TMDC and the substrate. We have found that the structural phase of the water influences the doping level and thus the tunneling barrier at the nanojunction. This leads to an increase in photocurrent and enhanced photopower generation., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Recruitment of receptors at membrane interfaces is essential in biological recognition and uptake processes. The interactions that induce recruitment are typically weak at the level of individual interaction pairs, but are strong and selective at the level of recruited ensembles. Here, a model system is demonstrated, based on the supported lipid bilayer (SLB) that mimics the recruitment process induced by weakly multivalent interactions. The weak (mm range) histidine-nickel-nitrilotriacetate (His 2 -NiNTA) pair is employed owing to its ease of implementation in both synthetic and biological systems. The recruitment of receptors (and ligands) induced by the binding of His 2 -functionalized vesicles on NiNTA-terminated SLBs is investigated to identify the ligand densities necessary to achieve vesicle binding and receptor recruitment. Threshold values of ligand densities appear to occur in many binding characteristics: density of bound vesicles, size and receptor density of the contact area, and vesicle deformation. Such thresholds contrast the binding of strongly multivalent systems and constitute a clear signature of the superselective binding behavior predicted for weakly multivalent interactions. This model system provides quantitative insight into the binding valency and effects of competing energetic forces, such as deformation, depletion, and entropy cost of recruitment at different length scales., (© 2023 The Authors. Small published by Wiley-VCH GmbH.)

There are numerous examples of materials that exhibit interesting phenomena at extremely low temperatures, but the difficulty of obtaining absolute zero at high pressure in experiments is sometimes a hurdle to reveal the exact explanation of these low temperature phenomena. Based on the calculations of the phonon spectrum and Gibbs free energy of α-N 2 and γ-N 2 under different pressures, we found that solid nitrogen at 0 K showed a re-entrant phase transition under continuously increasing pressure. The extremely low temperature in this pressure range turned out to be the main external condition for inducing phase transition as well as phase reversal.

Amyloid fibrils of the protein α-synuclein (αS) have recently been identified as a biomarker for Parkinson's disease (PD). To detect the presence of these amyloid fibrils, seed amplification assays (SAAs) have been developed. SAAs allow for the detection of αS amyloid fibrils in biomatrices such as cerebral spinal fluid and are promising for PD diagnosis by providing a dichotomous (yes/no) response. The additional quantification of the number of αS amyloid fibrils may enable clinicians to evaluate and follow the disease progression and severity. Developing quantitative SAAs has been shown to be challenging. Here, we report on a proof-of-principle study on the quantification of αS fibrils in fibril-spiked model solutions of increasing compositional complexity including blood serum. We show that parameters derived from standard SAAs can be used for fibril quantification in these solutions. However, interactions between the monomeric αS reactant that is used for amplification and biomatrix components such as human serum albumin have to be taken into account. We demonstrate that quantification of fibrils is possible even down to the single fibril level in a model sample consisting of fibril-spiked diluted blood serum.

A series of cyclomatrix polyphosphazene films have been prepared by nonaqueous interfacial polymerization (IP) of small aromatic hydroxyl compounds in a potassium hydroxide dimethylsulfoxide solution and hexachlorocyclotriphosphazene in cyclohexane on top of ceramic supports. Via the amount of dissolved potassium hydroxide, the extent of deprotonation of the aromatic hydroxyl compounds can be changed, in turn affecting the molecular structure and permselective properties of the thin polymer networks ranging from hydrogen/oxygen barriers to membranes with persisting hydrogen permselectivities at high temperatures. Barrier films are obtained with a high potassium hydroxide concentration, revealing permeabilities as low as 9.4 × 10 -17 cm 3 cm cm -2 s -1 Pa -1 for hydrogen and 1.1 × 10 -16 cm 3 cm cm -2 s -1 Pa -1 for oxygen. For films obtained with a lower concentration of potassium hydroxide, single gas permeation experiments reveal a molecular sieving behavior, with a hydrogen permeance of around 10 -8 mol m -2 s -1 Pa -1 and permselectivities of H 2 /N 2 (52.8), H 2 /CH 4 (100), and H 2 /CO 2 (10.1) at 200 °C., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

High-impedance resonators are a promising contender for realizing long-distance entangling gates between spin qubits. Often, the fabrication of spin qubits relies on the use of gate dielectrics which are detrimental to the quality of the resonator. Here, we investigate loss mechanisms of high-impedance NbTiN resonators in the vicinity of thermally grown SiO 2 and Al 2 O 3 fabricated by atomic layer deposition. We benchmark the resonator performance in elevated magnetic fields and at elevated temperatures and find that the internal quality factors are limited by the coupling between the resonator and two-level systems of the employed oxides. Nonetheless, the internal quality factors of high-impedance resonators exceed 10 3 in all investigated oxide configurations which implies that the dielectric configuration would not limit the performance of resonators integrated in a spin-qubit device. Because these oxides are commonly used for spin qubit device fabrication, our results allow for straightforward integration of high-impedance resonators into spin-based quantum processors. Hence, these experiments pave the way for large-scale, spin-based quantum computers., Competing Interests: Competing interestsThe authors declare no competing interests., (© Springer-Verlag GmbH Germany, part of Springer Nature 2023.)

We present a quantitative study of the density of states (DOS) in SF bilayers (where S is a bulk superconductor and F is a ferromagnetic metal) in the diffusive limit. We solve the quasiclassical Usadel equations in the structure considering the presence of magnetic and spin-orbit scattering. For practical reasons, we propose the analytical solution for the density of states in SF bilayers in the case of a thin ferromagnet and low transparency of the SF interface. This solution is confirmed by numerical calculations using a self-consistent two-step iterative method. The behavior of DOS dependencies on magnetic and spin-orbit scattering times is discussed., (Copyright © 2022, Karabassov et al.)

Since the start of the COVID-19 pandemic, 10 manufacturers of molecular tests for SARS-CoV-2 have received Emergency Use Authorizations from the U.S. Food and Drug Administration for point-of-care or over the counter use. In this review, the working principle of these tests is described as well as the relevant characteristics (e.g. time-to-result and specimen type). The analytical (e.g. analytical sensitivity) and clinical performance (positive and negative percent agreement) and useability characteristics (e.g. cost, reusability and throughput) of these tests are compared and critically reviewed. Also details for relevant respiratory multiplex assays of these 10 manufacturers are discussed. Critical review of scientific literature on these authorized tests revealed that for many of these tests publications are almost or completely absent, with the exception of two systems. The Xpert Xpress has been thoroughly investigated and good performance has been reported, whereas ID NOW is also well-represented in literature, but has relatively low sensitivity., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

We report the design and one-pot synthesis of Ag-doped BiVO 4 embedded in reduced graphene oxide (BiVO 4 :Ag/rGO) nanocomposites via a hydrothermal processing route. The binary heterojunction photocatalysts exhibited high efficiency for visible light degradation of model dyes and were correspondingly used for the preparation of photocatalytic membranes using polyvinylidene fluoride (PVDF) or polyethylene glycol (PEG)-modified polyimide (PI), respectively. The surface and cross-section images combined with elemental mapping illustrated the effective distribution of the nanocomposites within the polymeric membranes. Photocatalytic degradation efficiencies of 61% and 70% were achieved after 5 h of visible light irradiation using BiVO 4 :Ag/rGO@PVDF and BiVO 4 :Ag/rGO@PI (PEG-modified) systems, respectively. The beneficial photocatalytic performance of the BiVO 4 :Ag/rGO@PI (PEG-modified) membrane is explained by the higher hydrophilicity due to the PEG modification of the PI membrane. This work may provide a rational and effective strategy to fabricate highly efficient photocatalytic nanocomposite membranes with well-contacted interfaces for environmental purification., (© 2022 IOP Publishing Ltd.)

Encapsulation of multiple adjuvants along with antigens into nanocarriers allows a co-delivery to antigen-presenting cells for the synergistic induction of robust immune responses. However, loading cargoes of different molar masses, polarities, and solubilities in high efficiencies remains a challenge. Therefore, we developed a strategy to encapsulate a triple combination of the so-called adjuvants, i.e. with Resiquimod (R848), muramyl dipeptide (MDP) and polyinosinic-polycytidylic acid (Poly(I : C)) into human serum albumin (HSA) nanocarriers. The loading is conducted in situ while the nanocarrier is formed by an orthogonal and metal-free click reaction at the interface of an inverse miniemulsion. By this unique approach, high encapsulation efficiency without harming the cargo during the nanocarrier formation process and regardless of their physical properties is achieved, thus keeping their bioactivity. Furthermore, we demonstrated high control over the encapsulation efficiency and varying the amount of each cargo did not influence the efficiency of multicomponent encapsulation. Azide-modified HSA was crosslinked with hexanediol dipropiolate (HDDP) at the interface of a water-in-oil miniemulsion. Varying the crosslinker amount allowed us to tailor the density and degradation rates of the protein shell. Additional installation of disulfide bonds into the crosslinker created redox-responsive nanocarriers, which degraded both by protease and under reducing conditions with dithiothreitol. The prepared HSA nanocarriers were efficiently taken up by dendritic cells and exhibited an additive cell activation and maturation, exceeding the nanocarriers loaded with only a single drug. This general protocol allows the orthogonal and metal-free encapsulation of various drugs or adjuvants at defined concentrations into the protein nanocarriers.

An industrial ceramic nanofiltration membrane (pore size 0.9 nm) was tested in a Canadian oil field for more than 12,500 h to treat wastewater directly from daily operations, without any type of pre-treatment. This wastewater contained a high content of total suspended solids (13 to 510 mg/kg), and total organic carbon (31 to 134 mg/kg). The membrane unit was operated at different transmembrane pressure (TMP) set points (4-16 bar) and recovery set points (40-80%). The data show that ion and compound rejection depend strongly on a combination of both TMP and recovery, with the largest rejection occurring at low recovery values and high TMP values. Two mechanisms were responsible for rejection: sieving, which mostly impacted compound rejection, and electrostatic phenomena that impacted ion rejection. It is shown that ion rejection depends linearly on charge density of the ion. Ion rejection was measured as high as 85% and compounds (such as TSS) were rejected as high as 100%. The specific flux varied between 1-10 L/(m 2 .h.bar). Results from this field testing indicate the possibility of using these types of ceramic membranes for oil field wastewater treatment., (Copyright © 2022. Published by Elsevier Ltd.)

We embarked on an in situ low-energy electron microscopy, photo-electron emission microscopy, and selected area low-energy electron diffraction study during the cooling of huge eutectic droplets through the critical stages of the eutectic transition. On this journey through uncharted waters, we revealed an expected initial shrinking of the exposed area of the droplet, followed by an unanticipated expansion. We attribute this behavior to an initial fast amorphization of the interface between the droplet and surface, followed by the recrystallization of Ge expelled from the droplet at the interface. As a major surprise, we discovered the emergence of extensive "spaghetti"-like patterns, which are rationalized in terms of parallel Ge ripples oriented along, mainly, [-554] and [-55-4] directions. They emerge during spinodal decomposition when passing the eutectic temperature of the system. Their sides are defined by Ge{111} and Ge{11-1} vicinals covered with Pt-modified (√3 × √3) superstructures. The distance between adjacent ripples is about 18 nm., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Germanium sulfide (GeS) is a layered monochalcogenide semiconductor with a band gap of about 1.6 eV. To verify the suitability of GeS for field-effect-based device applications, a detailed understanding of the electronic transport mechanisms of GeS-metal junctions is required. In this work, we have used conductive atomic force microscopy (c-AFM) to study charge carrier injection in metal-GeS nanocontacts. Using contact current-voltage spectroscopy, we identified three dominant charge carrier injection mechanisms: thermionic emission, direct tunneling, and Fowler-Nordheim tunneling. In the forward-bias regime, thermionic emission is the dominating current injection mechanism, whereas in the reverse-bias regime, the current injection mechanism is quantum mechanical tunneling. Using tips of different materials (platinum, n-type-doped silicon, and highly doped p-type diamond), we found that the Schottky barrier is almost independent of the work function of the metallic tip, which is indicative of a strong Fermi-level pinning. This strong Fermi-level pinning is caused by charged defects and impurities., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Monitoring the performance of polymer-functionalized surfaces that aim at removing and inactivating viruses is typically labor-intensive and time-consuming. This hampers the development and optimization of such surfaces. Here we present experiments of low complexity that can be used to characterize and quantify the antiviral properties of polymer-functionalized surfaces. We showcase our approach on polyethylenimine (PEI)-coated poly(ether sulfone) (PES) microfiltration membranes. We use a fluorescently labeled model virus to quantify both virus removal and inactivation. We directly quantify the log removal of intact viruses by this membrane using single particle counting. Additionally, we exploit the change in photophysical properties upon disassembly of the virus to show that viruses are inactivated by the PEI coating. Although only a small fraction of intact viruses can pass the membrane, a considerable fraction of inactivated, disassembled viruses are found in the filtrate. Fluorescence microscopy experiments show that most of the viruses left behind on the microfiltration membrane are in the inactivated, disassembled state. Combined, our fluorescence microscopy and spectroscopy experiments show that not only does the model virus adsorb to the PEI coating on the membrane but also the interaction with PEI results in the disassembly of the virus capsid., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)