Browse Articles

Concurrent loss of the Y chromosome in cancer and T cells impacts outcome

Daily electric field treatment improves functional outcomes after thoracic contusion spinal cord injury in rats

Abstract Spinal cord injury (SCI) can cause permanent loss of sensory, motor, and autonomic functions, with limited therapeutic options available. Low-frequency electric fields with changing polarity have shown promise in promoting axon regeneration and improving outcomes. However, the metal electrodes used previously were prone to corrosion, and their epidural placement limited the penetration of the electric field into the spinal cord. Here, we demonstrate that a thin-film implant with supercapacitive electrodes placed under the dura mater can safely and effectively deliver electric field treatment in rats with thoracic SCI. Subdural stimulation enhanced hind limb function and touch sensitivity compared to controls, without inducing a neuroinflammatory response in the spinal cord. While axon density around the lesion site remained unchanged after 12 weeks, in vivo monitoring and electrochemical testing of electrodes indicated that treatment was administered throughout the study. These results highlight the promise of electric field treatment as a viable therapeutic strategy for achieving long-term functional recovery in SCI.

Doublet decoding of tRNASer3 demonstrates plasticity of ribosomal decoding center

Abstract Frameshifts can be caused by specific combinations of tRNA and mRNA. The wildtype AGC-decoding E. coli tRNASer3 GCU has been shown to induce −1 ribosomal frameshifting on GCA alanine codons, and proposed to read a two-base codon instead of a canonical triplet. However, it has remained unclear whether this type of non-cognate decoding can be accommodated by the ribosome. Here, we perform single-particle cryo-EM reconstructions on E. coli 70S ribosomes with the frameshift-inducing tRNASer3 bound to the non-cognate GCA codon or the cognate AGC codon in the ribosomal A site. The structures demonstrate that doublet decoding is made possible when A1493, the conserved monitoring base in 16S rRNA, mimics a first codon base, forming a Hoogsteen base pair with U36 from the anticodon and stacking with the mRNA. This interaction pushes the first two bases of the A-site codon in position for base pairing with C35 and G34 of the anticodon.

Integrin beta 1 facilitates non-enveloped hepatitis E virus cell entry through the recycling endosome

Abstract Hepatitis E virus (HEV) is a major cause of acute hepatitis and mainly transmitted faecal-orally. HEV particles present in faeces are naked (nHEV), whereas those found in the blood are quasi-enveloped (eHEV) with a cell-derived lipid membrane. Despite its global health impact, the cellular life cycle of HEV remains poorly understood, particularly regarding the mechanisms of viral entry into host cells. To address this knowledge gap, we develop a high content RNA-FISH-based imaging assay that allows for the investigation of the entry pathways of both naked and quasi-enveloped HEV particles. Surprisingly, we find that integrin α3, previously implicated in nHEV cell entry, is not expressed in the cell types that are most permissive for HEV infection. Instead, we identify integrin β1 (ITGB1) pairing with different α-integrins as the key player mediating nHEV cell entry. Our results indicate that the interaction of nHEV with ITGB1 facilitates entry through Rab11-positive recycling endosomes. In contrast, eHEV particles do not interact with ITGB1 and enter cells using a classical endocytic route via Rab5a-positive early endosomes. The entry of both types of HEV particles requires endosomal acidification and proteolytic cleavage by lysosomal cathepsins, which ultimately results in delivery of the HEV genome to the cytoplasm.

Author Correction: Reconstruction of human dispersal during Aurignacian on pan-European scale

Author Correction: Mitochondrion-specific dendritic lipopeptide liposomes for targeted sub-cellular delivery

Coherent bunching of anyons and dissociation in an interference experiment

A soft-clamped topological waveguide for phonons

Don’t sleepwalk from computer-vision research into surveillance

Eureka! The brain science behind lightbulb moments

Evidence of Coulomb liquid phase in few-electron droplets

Abstract Emergence of universal collective behaviour from interactions within a sufficiently large group of elementary constituents is a fundamental scientific concept1. In physics, correlations in fluctuating microscopic observables can provide key information about collective states of matter, such as deconfined quark–gluon plasma in heavy-ion collisions2 or expanding quantum degenerate gases3,4. Mesoscopic colliders, through shot-noise measurements, have provided smoking-gun evidence on the nature of exotic electronic excitations such as fractional charges5,6, levitons7 and anyon statistics8. Yet, bridging the gap between two-particle collisions and the emergence of collectivity9 as the number of interacting particles increases10 remains a challenging task at the microscopic level. Here we demonstrate all-body correlations in the partitioning of electron droplets containing up to N = 5 electrons, driven by a moving potential well through a Y-junction in a semiconductor device. Analysing the partitioning data using high-order multivariate cumulants and finite-size scaling towards the thermodynamic limit reveals distinctive fingerprints of a strongly correlated Coulomb liquid. These fingerprints agree well with a universal limit at which the partitioning of a droplet is predicted by a single collective variable. Our electron-droplet scattering experiments illustrate how coordinated behaviour emerges through interactions of only a few elementary constituents. Studying similar signatures in other physical platforms such as cold-atom simulators4,11 or collections of anyonic excitations8,12 may help identify emergence of exotic phases and, more broadly, advance understanding of matter engineering.

We need to predict the people disasters will hit, not just the places

‘Harm’ must not be redefined by US conservation agencies

How to make America healthy: the real problems — and best fixes

Adversarial collaborations: all theories must be subject to critical evaluation

Divergent DNA methylation dynamics in marsupial and eutherian embryos

Abstract Based on seminal work in placental species (eutherians) 1–10 , a paradigm of mammalian development has emerged wherein the genome-wide erasure of parental DNA methylation is required for embryogenesis. Whether such DNA methylation reprogramming is, in fact, conserved in other mammals is unknown. Here, to resolve this point, we generated base-resolution DNA methylation maps in gametes, embryos and adult tissues of a marsupial, the opossum Monodelphis domestica , revealing variations from the eutherian-derived model. The difference in DNA methylation level between oocytes and sperm is less pronounced than that in eutherians. Furthermore, unlike the genome of eutherians, that of the opossum remains hypermethylated during the cleavage stages. In the blastocyst, DNA demethylation is transient and modest in the epiblast. However, it is sustained in the trophectoderm, suggesting an evolutionarily conserved function for DNA hypomethylation in the mammalian placenta. Furthermore, unlike that in eutherians, the inactive X chromosome becomes globally DNA hypomethylated during embryogenesis. We identify gamete differentially methylated regions that exhibit distinct fates in the embryo, with some transient, and others retained and that represent candidate imprinted loci. We also reveal a possible mechanism for imprinted X inactivation, through maternal DNA methylation of the Xist-like noncoding RNA RSX 11 . We conclude that the evolutionarily divergent eutherians and marsupials use DNA demethylation differently during embryogenesis.

Make the study of human flourishing a global priority

In the face of anti-science politics, silence is not without cost

Celebrating the anniversary of Michael Faraday’s discovery of benzene

A distributed coding logic for thermosensation and inflammatory pain

Abstract Somatosensory neurons encode detailed information about touch and temperature and are the peripheral drivers of pain1,2. Here by combining functional imaging with multiplexed in situ hybridization3, we determined how heat and mechanical stimuli are encoded across neuronal classes and how inflammation transforms this representation to induce heat hypersensitivity, mechanical allodynia and continuing pain. Our data revealed that trigeminal neurons innervating the cheek exhibited complete segregation of responses to gentle touch and heat. By contrast, heat and noxious mechanical stimuli broadly activated nociceptor classes, including cell types proposed to trigger select percepts and behaviours4–6. Injection of the inflammatory mediator prostaglandin E2 caused long-lasting activity and thermal sensitization in select classes of nociceptors, providing a cellular basis for continuing inflammatory pain and heat hypersensitivity. We showed that the capsaicin receptor TRPV1 (ref. 7) has a central role in heat sensitization but not in spontaneous nociceptor activity. Unexpectedly, the responses to mechanical stimuli were minimally affected by inflammation, suggesting that tactile allodynia results from the continuing firing of nociceptors coincident with touch. Indeed, we have demonstrated that nociceptor activity is both necessary and sufficient for inflammatory tactile allodynia. Together, these findings refine models of sensory coding and discrimination at the cellular and molecular levels, demonstrate that touch and temperature are broadly but differentially encoded across transcriptomically distinct populations of sensory cells and provide insight into how cellular-level responses are reshaped by inflammation to trigger diverse aspects of pain.