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TiO-supported catalysts with ZnO and ZrO for non-oxidative dehydrogenation of propane: mechanistic analysis and application potential
No full textNon-oxidative dehydrogenation of propane is one of the most promising technologies for propene production in terms of environmental impact and sustainability. The purpose of the present study was to develop environmentally friendly and low-cost catalysts alternatives to current applied Pt- or CrOx-based catalysts. Rutile TiO2-based catalysts with supported ZnOx and ZrOx species were established to show promising performance under industrially relevant conditions. The amount of propene produced within 3 h on propane stream at 550°C over the optimized catalyst with 2 wt% Zn and 5.6 wt% Zr is close to that obtained over commercial-like K-CrOx/Al2O3 and the state-of-the-art Cu/YZrOx catalyst. The selectivity to propene over our catalyst was about 95% at a propane conversion of about 23%. The kind of active sites and the effect of ZrO2 addition on catalyst performance and physicochemical properties were elucidated owing to the application of complementary characterisation techniques such as XRD, N2 physisorption, HRTEM, EDX, XPS, X-ray absorption spectroscopy, NH3-TPD, CO-TPR, Raman and O2-TPO. ZnOx clusters with 1-3 Zn atoms were concluded to be the active sites. ZrO2 enhances their intrinsic activity and inhibits the formation of inactive rhombohedral ZnTiO3 phase
Binding specificities of human RNA-binding proteins toward structured and linear RNA sequences
No full textRNA-binding proteins (RBPs) regulate RNA metabolism at multiple levels by affecting splicing of nascent transcripts, RNA folding, base modification, transport, localization, translation, and stability. Despite their central role in RNA function, the RNA-binding specificities of most RBPs remain unknown or incompletely defined. To address this, we have assembled a genome-scale collection of RBPs and their RNA-binding domains (RBDs) and assessed their specificities using high-throughput RNA-SELEX (HTR-SELEX). Approximately 70% of RBPs for which we obtained a motif bound to short linear sequences, whereas ∼30% preferred structured motifs folding into stem–loops. We also found that many RBPs can bind to multiple distinctly different motifs. Analysis of the matches of the motifs in human genomic sequences suggested novel roles for many RBPs. We found that three cytoplasmic proteins—ZC3H12A, ZC3H12B, and ZC3H12C—bound to motifs resembling the splice donor sequence, suggesting that these proteins are involved in degradation of cytoplasmic viral and/or unspliced transcripts. Structural analysis revealed that the RNA motif was not bound by the conventional C3H1 RNA-binding domain of ZC3H12B. Instead, the RNA motif was bound by the ZC3H12B's PilT N terminus (PIN) RNase domain, revealing a potential mechanism by which unconventional RBDs containing active sites or molecule-binding pockets could interact with short, structured RNA molecules. Our collection containing 145 high-resolution binding specificity models for 86 RBPs is the largest systematic resource for the analysis of human RBPs and will greatly facilitate future analysis of the various biological roles of this important class of proteins
Structural and functional characterization of the severe fever with thrombocytopenia syndrome virus L protein
No full textThe Bunyavirales order contains several emerging viruses with high epidemic potential, including Severe fever with thrombocytopenia syndrome virus (SFTSV). The lack of medical countermeasures, such as vaccines and antivirals, is a limiting factor for the containment of any virus outbreak. To develop such antivirals a profound understanding of the viral replication process is essential. The L protein of bunyaviruses is a multi-functional and multi-domain protein performing both virus transcription and genome replication and, therefore, is an ideal drug target. We established expression and purification procedures for the full-length L protein of SFTSV. By combining single-particle electron cryo-microscopy and X-ray crystallography, we obtained 3D models covering ∼70% of the SFTSV L protein in the apo-conformation including the polymerase core region, the endonuclease and the cap-binding domain. We compared this first L structure of the Phenuiviridae family to the structures of La Crosse peribunyavirus L protein and influenza orthomyxovirus polymerase. Together with a comprehensive biochemical characterization of the distinct functions of SFTSV L protein, this work provides a solid framework for future structural and functional studies of L protein–RNA interactions and the development of antiviral strategies against this group of emerging human pathogens
pH stability and disassembly mechanism of wild-type simian virus 40
No full textViruses are remarkable self-assembled nanobiomaterial-based machines, exposed to a wide range of pH values. Extreme pH values can induce dramatic structural changes, critical for the function of the virus nanoparticles, including assembly and genome uncoating. Tuning cargo–capsid interactions is essential for designing virus-based delivery systems. Here we show how pH controls the structure and activity of wild-type simian virus 40 (wtSV40) and the interplay between its cargo and capsid. Using cryo-TEM and solution X-ray scattering, we found that wtSV40 was stable between pH 5.5 and 9, and only slightly swelled with increasing pH. At pH 3, the particles aggregated, while capsid protein pentamers continued to coat the virus cargo but lost their positional correlations. Infectivity was only partly lost after the particles were returned to pH 7. At pH 10 or higher, the particles were unstable, lost their infectivity, and disassembled. Using time-resolved experiments we discovered that disassembly began by swelling of the particles, poking a hole in the capsid through which the genetic cargo escaped, followed by a slight shrinking of the capsids and complete disassembly. These findings provide insight into the fundamental intermolecular forces, essential for SV40 function, and for designing virus-based nanobiomaterials, including delivery systems and antiviral drugs
Orthogonal Techniques to Study the Effect of pH, Sucrose, and Arginine Salts on Monoclonal Antibody Physical Stability and Aggregation During Long-Term Storage
No full textUnderstanding the effects of additives on therapeutic protein stability is of paramount importance for obtaining stable formulations. In this work, we apply several high- and medium-throughput methods to study the physical stability of a model monoclonal antibody at pH 5.0 and 6.5 in the presence of sucrose, arginine hydrochloride, and arginine glutamate. In low ionic strength buffer, the addition of salts reduces the antibody colloidal and thermal stability, attributed to screening of electrostatic interactions. The presence of glutamate ion in the arginine salt partially reduces the damaging effect of ionic strength increase. The addition of 280 mM sucrose shifts the thermal protein unfolding to a higher temperature. Arginine salts in the used concentration reduce the relative monomer yield after refolding from urea, whereas sucrose has a favorable effect on antibody refolding. In addition, we show 12-month long-term stability data and observe correlations between thermal protein stability, relative monomer yield after refolding, and monomer loss during storage. The monomer loss during storage is related to protein aggregation and formation of subvisible particles in some of the formulations. This study shows that the effect of commonly used additives on the long-term antibody physical stability can be predicted using orthogonal biophysical measurements
A concordance scenario for the observation of a neutrino from the Tidal Disruption Event AT2019dsg
No full textWe introduce a phenomenological concordance scenario with a relativistic jet for the Tidal Disruption Event (TDE) AT2019dsg, which has been proposed as source of the astrophysical neutrino event IceCube-191001A. Noting that AT2019dsg is one of the brightest (and few) TDEs observed in X-rays, we connect the neutrino production with the X-rays: an expanding cocoon causes the progressive obscuration of the X-rays emitted by the accretion disk, while at the same time it provides a sufficiently intense external target of back-scattered X-rays for photo-pion production off protons. We also describe the late-term emission of the neutrino (about 150 days after the peak), by scaling the production radius with the black body radius. Our energetics and assumptions for the jet and the cocoon are compatible with expectations from numerical simulations of TDEs. We predict 0.26 neutrino events in the right energy range in IceCube
Revealing the structure of composite nanodiamond–graphene oxide aqueous dispersions by small-angle scattering
No full textThe work presents the results of studying the structure of binary liquid nanocarbon systems obtained by mixing hydrosol of detonation nanodiamond and aqueous dispersions of single layer graphene oxide flakes. We studied size and space distribution of nanocarbon clusters formed upon interaction of the components in aqueous media by mutually complement methods of small-angle X-ray and neutron scattering. The formation of small secondary agglomerates of nanodiamond particles on the surface of graphene oxide flakes was concluded and supported by the data of transmission electron microscopy from dried samples. The observed effect can significantly modify the structure of nanocarbon composites formed of nanodiamond and graphene oxide. The structural features of binary dispersions detonation nanodiamond–graphene oxide should be taken into account at the preparation of the conductive composites of reduced graphene oxide for energy storage systems
Načrtovanje de novo proteinskega konformacijskega stikala na osnovi motiva ovite vijačnice
No full textDe novo protein design represents an exciting opportunity to explore the conformational space unsampled by nature and develop novel protein folds and functionality. One of the current challenges in the protein design field is the design of proteins that change their conformation in response to environmental cues. Conformational change of proteins in response to chemical or physical signals is the underlying principle of many regulatory and transport mechanisms in biological systems. The ability to design proteins whose conformational state can be precisely and reversibly controlled would facilitate the development of smart bio-inspired materials or molecular machines tailored for specific applications. We explored metal-binding site design to engineer peptide-based conformational switches that assemble into a dimeric coiled-coil in response to the addition of Zn(II) ions. Coiled-coil dimers are present in many natural proteins and have been used to construct synthetic protein nanostructures. Firstly, we designed a peptide called SwitCCh that formed a parallel homodimeric coiled-coil in the presence of Zn(II) or low pH. The addition of Zn(II) promoted formation of a parallel homodimer with an increase in thermal stability by more than 30 °C. The peptide could be reversibly cycled between the coiled-coil and random conformation. Furthermore, the SwitCCh peptide was orthogonal to the previously developed coiled-coil dimer set, indicating it could be used for regulated self-assembly of coiled-coil based nanostructures and materials. We further advanced our work by utilizing metal-binding site design to render a previously designed orthogonal set of coiled-coil heterodimers Zn(II)-responsive. Circular dichroism spectroscopy and size exclusion chromatography coupled to multi-angle light scattering confirmed the designed peptides assembled into coiled-coil heterodimers only in the presence of Zn(II). Additionally, designed peptides also acted as pH switches, since low pH prevented coordination of Zn(II) and lead to disassembling of coiled-coils. Our results showed the incorporation of a metal binding site not only preserved orthogonality, but that it is also a viable strategy for increasing the size of orthogonal sets. The designed Zn(II)-responsive coiled-coils were used for the construction of a triangular fold, whose assembly and disassembly was under the control of Zn(II) ions, demonstrating the designed set could facilitate the development of coiled-coil protein cages with easily controllable folding and unfolding
Study of central exclusive production in proton-proton collisions at 5.02 and 13 TeV
No full textCentral exclusive and semiexclusive production of pairs is measured with the CMS detector in proton-proton collisions at the LHC at center-of-mass energies of 5.02 and 13TeV. The theoretical description of these nonperturbative processes, which have not yet been measured in detail at the LHC, poses a significant challenge to models. The two pions are measured and identified in the CMS silicon tracker based on specific energy loss, whereas the absence of other particles is ensured by calorimeter information. The total and differential cross sections of exclusive and semiexclusive central production are measured as functions of invariant mass, transverse momentum, and rapidity of the system in the fiducial region defined as transverse momentum > 0.2 GeV and pseudorapidity < 2.4. The production cross sections for the four resonant channels (500), (770), (980), and (1270) are extracted using a simple model. These results represent the first measurement of this process at the LHC collision energies of 5.02 and 13TeV
Robust cosmological constraints on axion-like particles
No full textAxion-like particles with masses in the keV-GeV range have a profound impact on the cosmological evolution of our Universe, in particular on the abundance of light elements produced during Big Bang Nucleosynthesis. The resulting limits are complementary to searches in the laboratory and provide valuable additional information regarding the validity of a given point in parameter space. A potential drawback is that altering the cosmological history may potentially weaken or even fully invalidate these bounds. The main objective of this article is therefore to evaluate the robustness of cosmological constraints on axion-like particles in the keV-GeV region, allowing for various additional effects which may weaken the bounds of the standard scenario. Employing the latest determinations of the primordial abundances as well as information from the cosmic microwave background we find that while bounds can indeed be weakened, very relevant robust constraints remain