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While RNA has recently been recognized as an interesting small-molecule drug target, many challenges remain to be addressed before we take full advantage of it. This emphasizes the necessity to improve our understanding of its structures and functions. Over the years, sequencing technologies have produced an enormous amount of unlabeled RNA data, which hides a huge potential. Motivated by the successes of protein language models, we introduce RiboNucleic Acid Language Model (RiNALMo) to unveil the hidden code of RNA. RiNALMo is the largest RNA language model to date, with 650M parameters pre-trained on 36M non-coding RNA sequences from several databases. It can extract hidden knowledge and capture the underlying structure information implicitly embedded within the RNA sequences. RiNALMo achieves state-of-the-art results on several downstream tasks. Notably, we show that its generalization capabilities overcome the inability of other deep learning methods for secondary structure prediction to generalize on unseen RNA families. RiNALMo, a large-scale RNA language model trained on non-coding RNA sequences, captures structural information and achieves state-of-the-art performance on multiple tasks, notably generalizing to unseen RNA families in secondary structure prediction.

Interferometry reveals quantized changes in the angular momentum of neutrons that have been ‘twisted’ by passage through a spiral staircase structure. Orbital angular momentum control in neutron optics Orbital angular momentum is a quantized degree of freedom exploited in many applications. The photon orbital angular momentum has been used in fundamental tests of quantum mechanics and imaging and the electron orbital angular momentum has proven useful for determining the chirality of crystals. But the phenomenon had not previously been demonstrated in neutrons. Here Dmitry Pushin and colleagues show how to control orbital angular momentum states in a neutron beam through the use of macroscopic spiral phase plates. After applying this 'twist' to an input neutron beam, the quantized orbital angular momentum of neutrons is characterized by neutron interferometry. In contrast to photons and electrons, neutrons are massive particles, hence this result could open important new perspectives for testing quantum mechanics with massive observables. In addition, the neutron orbital angular momentum could enable new approaches for neutron scattering techniques. The quantized orbital angular momentum (OAM) of photons 1 offers an additional degree of freedom and topological protection from noise. Photonic OAM states have therefore been exploited in various applications 2 , 3 ranging from studies of quantum entanglement and quantum information science 4 , 5 , 6 , 7 to imaging 8 , 9 , 10 , 11 , 12 . The OAM states of electron beams 13 , 14 , 15 have been shown to be similarly useful, for example in rotating nanoparticles and determining the chirality of crystals 16 , 17 , 18 , 19 . However, although neutrons—as massive, penetrating and neutral particles—are important in materials characterization, quantum information and studies of the foundations of quantum mechanics, OAM control of neutrons has yet to be achieved. Here, we demonstrate OAM control of neutrons using macroscopic spiral phase plates that apply a ‘twist’ to an input neutron beam. The twisted neutron beams are analysed with neutron interferometry. Our techniques, applied to spatially incoherent beams, demonstrate both the addition of quantum angular momenta along the direction of propagation, effected by multiple spiral phase plates, and the conservation of topological charge with respect to uniform phase fluctuations. Neutron-based studies of quantum information science 20 , 21 , the foundations of quantum mechanics 22 , 23 , and scattering and imaging 24 of magnetic, superconducting and chiral materials have until now been limited to three degrees of freedom: spin, path and energy. The optimization of OAM control, leading to well defined values of OAM, would provide an additional quantized degree of freedom for such studies.

Spin-orbit coupling of light has come to the fore in nanooptics and plasmonics, and is a key ingredient of topological photonics and chiral quantum optics. We demonstrate a basic tool for incorporating analogous effects into neutron optics: the generation and detection of neutron beams with coupled spin and orbital angular momentum. The ³He neutron spin filters are used in conjunction with specifically oriented triangular coils to prepare neutron beams with lattices of spin-orbit correlations, as demonstrated by their spin-dependent intensity profiles. These correlations can be tailored to particular applications, such as neutron studies of topological materials.

As quantum information technologies advance, challenges in scaling and connectivity persist, particularly the need for long-range qubit connectivity and efficient entanglement generation. Perfect State Transfer enables time-optimal state transfer between distant qubits using only nearest-neighbor couplings, enhancing device connectivity. Moreover, the transfer protocol results in effective parity-dependent non-local interactions, extending its utility to entanglement generation. Here, we experimentally demonstrate Perfect State Transfer and multi-qubit entanglement generation on a chain of six superconducting transmon qubits with tunable couplers, controlled via parametric drives. By simultaneously activating and engineering all couplings, we implement the transfer for up to six qubits, verifying single-excitation dynamics for different initial states. Extending the protocol to multiple excitations, we confirm its parity-dependent nature, where excitation number controls the phase of the transferred state. Finally, leveraging this property, we prepare a Greenberger-Horne-Zeilinger state using a single transfer operation, showcasing potential of Perfect State Transfer for efficient entanglement generation. Perfect State Transfer is known to time-optimally connect distant nodes in a network. Here, the authors implement it on a chain of superconducting qubits and demonstrate that it also serves as a powerful tool for generating multi-qubit entanglement.

SARS-CoV-2 is a major threat to global health. Here, we investigate the RNA structure and RNA-RNA interactions of wildtype (WT) and a mutant (Δ382) SARS-CoV-2 in cells using Illumina and Nanopore platforms. We identify twelve potentially functional structural elements within the SARS-CoV-2 genome, observe that subgenomic RNAs can form different structures, and that WT and Δ382 virus genomes fold differently. Proximity ligation sequencing identify hundreds of RNA-RNA interactions within the virus genome and between the virus and host RNAs. SARS-CoV-2 genome binds strongly to mitochondrial and small nucleolar RNAs and is extensively 2’-O-methylated. 2’-O-methylation sites are enriched in viral untranslated regions, associated with increased virus pair-wise interactions, and are decreased in host mRNAs upon virus infection, suggesting that the virus sequesters methylation machinery from host RNAs towards its genome. These studies deepen our understanding of the molecular and cellular basis of SARS-CoV-2 pathogenicity and provide a platform for targeted therapy. Here, Yang et al. apply different RNA sequencing approaches to characterize the secondary structure of SARS-CoV-2 viral RNAs, report on long-range interactions along the viral genome, and uncover the virus-host RNA interactome in cells.

Robust manufacturing processes resulting in consistent glycosylation are critical for the efficacy and safety of biopharmaceuticals. Information on glycosylation can be obtained by conventional bottom–up methods but is often limited to the glycan or glycopeptide level. Here, we apply high-resolution native mass spectrometry (MS) for the characterization of the therapeutic fusion protein Etanercept to unravel glycoform heterogeneity in conditions of hitherto unmatched mass spectral complexity. Higher spatial resolution at lower charge states, an inherent characteristic of native MS, represents a key component for the successful revelation of glycan heterogeneity. Combined with enzymatic dissection using a set of proteases and glycosidases, assignment of specific glycoforms is achieved by transferring information from subunit to whole protein level. The application of native mass spectrometric analysis of intact Etanercept as a fingerprinting tool for the assessment of batch-to-batch variability is exemplified and may be extended to demonstrate comparability after changes in the biologic manufacturing process. The specific glycosylation patterns of biological drugs often impact the efficacy and safety of the therapeutic product. Here the authors describe a native mass spectrometry approach that allows the resolution of highly complex glycosylation patterns on large proteins, which they apply to the therapeutic Fc-fusion protein Etanercept.

ObjectiveGlycation is a non-enzymatic and spontaneous post-translational modification (PTM) generated by the reaction between reducing sugars and primary amine groups within proteins. Because glycation can alter the properties of proteins, it is a critical quality attribute of therapeutic monoclonal antibodies (mAbs) and should therefore be carefully monitored. The most abundant product of glycation is formed by glucose and lysine side chains resulting in fructoselysine after Amadori rearrangement. In proteomics, which routinely uses a combination of chromatography and mass spectrometry to analyze PTMs, there is no straight-forward way to distinguish between glycation products of a reducing monosaccharide and an additional hexose within a glycan, since both lead to a mass difference of 162 Da.MethodsTo verify that the observed mass change is indeed a glycation product, we developed an approach based on 2D NMR spectroscopy spectroscopy and full-length protein samples denatured using high concentrations of deuterated urea.ResultsThe dominating β-pyranose form of the Amadori product shows a characteristic chemical shift correlation pattern in 1H-13C HSQC spectra suited to identify glucose-induced glycation. The same pattern was observed in spectra of a variety of artificially glycated proteins, including two mAbs, as well as natural proteins.ConclusionBased on this unique correlation pattern, 2D NMR spectroscopy can be used to unambiguously identify glucose-induced glycation in any protein of interest. We provide a robust method that is orthogonal to MS-based methods and can also be used for cross-validation.

The generation and control of neutron orbital angular momentum (OAM) states and spin correlated OAM (spin-orbit) states provides a powerful probe of materials with unique penetrating abilities and magnetic sensitivity. We describe techniques to prepare and characterize neutron spin-orbit states, and provide a quantitative comparison to known procedures. The proposed detection method directly measures the correlations of spin state and transverse momentum, and overcomes the major challenges associated with neutrons, which are low flux and small spatial coherence length. Our preparation techniques, utilizing special geometries of magnetic fields, are based on coherent averaging and spatial control methods borrowed from nuclear magnetic resonance. The described procedures may be extended to other probes such as electrons and electromagnetic waves.

There has been little research exploring the relationship between personality traits, self-esteem, and stigmatizing attitudes toward those with mental disorders. Furthermore, the mechanisms through which the beholder’s personality influence mental illness stigma have not been tested. The aim of this study is to examine the relationship between Big Five personality traits, self-esteem, familiarity, being a healthcare professional, and stigmatization. Moreover, this study aims to explore the mediating effect of perceived dangerousness on the relationship between personality traits and desire for social distance. We conducted a vignette-based representative population survey ( N  = 2207) in the canton of Basel-Stadt, Switzerland. Multiple regression analyses were employed to examine the associations between personality traits, self-esteem, familiarity, and being a healthcare professional with the desire for social distance and perceived dangerousness. The mediation analyses were performed using the PROCESS macro by Hayes. Analyses showed associations between personality traits and stigmatization towards mental illness. Those who scored higher on openness to experience ( β  = − 0.13, p  < 0.001), ( β  = − 0.14, p  < 0.001), and those who scored higher on agreeableness ( β  = − 0.15, p  < 0.001), ( β  = − 0.12, p  < 0.001) showed a lower desire for social distance and lower perceived dangerousness, respectively. Neuroticism ( β  = − 0.06, p  = 0.012) was inversely associated with perceived dangerousness. Additionally, high self-esteem was associated with increased stigmatization. Personal contact or familiarity with people having mental disorders was associated with decreased stigmatization. Contrarily, healthcare professionals showed higher perceived dangerousness ( β  = 0.04, p  = 0.040). Finally, perceived dangerousness partially mediated the association between openness to experience (indirect effect = −  .57, 95% CI [− .71, − 0.43]) as well as agreeableness (indirect effect = − 0.57, 95% CI [− 0.74, − 0.39]) and desire for social distance. Although the explained variance in all analyses is < 10%, the current findings highlight the role of personality traits and self-esteem in areas of stigma. Therefore, future stigma research and anti-stigma campaigns should take individual differences into consideration. Moreover, the current study suggests that perceived dangerousness mediates the relationship between personality traits and desire for social distance. Further studies are needed to explore the underlying mechanisms of such relationship. Finally, our results once more underline the necessity of increasing familiarity with mentally ill people and of improving the attitude of healthcare professionals towards persons with mental disorders.

Hydrogen (H2) was produced by aqueous-phase reforming of biomass-derived oxygenated hydrocarbons at temperatures near 500 kelvin over a tin-promoted Raney-nickel catalyst. The performance of this non-precious metal catalyst compares favorably with that of platinum-based catalysts for production of hydrogen from ethylene glycol, glycerol, and sorbitol. The addition of tin to nickel decreases the rate of methane formation from C-O bond cleavage while maintaining the high rates of C-C bond cleavage required for hydrogen formation.