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Travel efficiency in urban space: the role of built environment in shaping excess travel distance across transport modes
Reply to: Giant virus genomes are unlikely to be reservoirs of antibiotic resistance genes
Predictive risk assessment and targeted testing could enhance STI diagnosis in a high HIV prevalence setting in Eswatini
A multimodal deep fusion framework for highway traffic anomaly detection
Visualization of liquid-liquid phase transitions using a tiny G-quadruplex binding protein
Abstract Liquid-liquid phase transitions govern a wide range of protein-protein and protein-RNA interactions. Although the importance of multivalency and protein disorder in driving these transitions is clear, there is limited knowledge concerning the structural basis of phase transitions or the conformational changes that accompany this process. In this work, we found that a small human protein, SERF2, is important for the formation of stress granules. We determined the solution NMR structure ensemble of SERF2. We show that SERF2 specifically interacts with non-canonical tetrahelical RNA structures called G-quadruplexes, structures linked to stress granule formation. The biophysical amenability of both SERF2 and RNA G4 quadruplexes have allowed us to characterize the multivalent protein-RNA interactions involved in liquid-liquid phase transitions, the role that protein disorder plays in these transitions, identify the specific contacts involved, and describe how these interactions impact the structural dynamics of the components enabling a detailed understanding of the structural transitions involved in early stages of ribonucleoprotein condensate formation.
Sex-differences of survival and seasonal dispersal in a meta-population of greater horseshoe bats
External validity of cardiovascular risk assessment tools in individuals with MASLD (NAFLD): a cohort study
Solving the many-electron Schrödinger equation with a transformer-based framework
Risk prediction model development for requiring unplanned psychiatric readmission in bipolar disorder
A comprehensive application of FiveFold for conformation ensemble-based protein structure prediction
Biomimetic organo-hydrogels reveal the adipose tissue local mechanical anisotropy regulates ovarian cancer invasion
Abstract High-grade serous ovarian cancer, the most common and aggressive ovarian cancer subtype, frequently metastasises to visceral adipose tissues. In these tissues, the extracellular matrix through which ovarian cancer cells migrate is constrained by the presence and preponderance of adipocytes. How cells migrate in this unique environment is not known, yet critical to understanding metastatic progression. To study these processes, we developed biomimetic organo-hydrogels that recreate structural, mechanical, and biochemical properties of human adipose tissues. We show that ovarian cancer cells present invasive tropism towards organo-hydrogels, replicating the behaviour observed in native adipose tissues. This migration is facilitated by the mechanical anisotropy and microstructure of organo-hydrogels and adipose tissues, allowing the formation of migratory tracks. These results highlight the contribution of adipocytes to tissue biophysical features as a key regulatory factor of ovarian cancer cell migration and demonstrate that organo-hydrogels are particularly relevant tools to develop in vitro models of complex tissue architectures with high cellularity.
TRAP seq in 3D angiogenesis assays reveals a distinct endothelial translatome associated with early and late stages of morphogenesis
18β-Glycyrrhetinic acid inhibits the proliferation and metastasis of gastric cancer by inhibiting the TCTP/AKT/P53 signaling pathway
Ultrafast space-time optical merons in momentum-energy space
Multi-step organic synthesis, cytotoxicity, and molecular docking of new N-phenylpyrazolones incorporated with N-benzylthiazole or N-benzyl-4-thiazolone fragments
Hybridization as driving force for cryptic species diversity in the Caribbean coral genus Madracis
Impact of vaccination timing and coverage on measles near elimination dynamics: a mathematical modelling analysis
Abstract The Joint Committee for Vaccination and Immunisation recommended to implement an earlier second dose for the Measles-Mumps-Rubella (MMR) vaccine starting in 2026 in the United Kingdom. We investigated the impact of these changes on measles transmission in England. Using an age- and region-stratified mathematical model, we simulated outbreaks with different vaccination schedules and coverage, using electronic health records and outbreak data from 2010 to 2019. Delivering the second MMR dose at 24 months reduced cases by 11.86% (IQR: −3.3; 23.81%) compared to the current schedule (3 years and 4 months) and showed a 22.39% (IQR: 10.05; 32.79%) reduction of cases if achieving the same coverage as the first MMR dose. The effect of delivering an earlier second MMR was lower when waning of vaccine-induced immunity was included (5.28% (−10.92; 19.63%)). Increasing first-dose coverage by 0.5% annually yielded slightly better outcomes than an earlier second dose (14.68% reduction, IQR:1.19; 27.49.9%). While improving first-dose uptake had the greatest impact, it may be difficult to achieve. Thus, an earlier second MMR dose can be a feasible alternative to reduce the measles burden in England where measles transmission follows typical near-elimination dynamics.
Impact of shared spaces and daily routines on shared microbiome
The histone methyltransferase SETD2 regulates adult brain structure, connectivity and neurogenesis
Abstract Epigenetic mechanisms are crucial for neocortical development. Recent work has highlighted that ablation of Setd2, which encodes a SET domain lysine methyltransferase, from the mouse dorsal telencephalon results in deficits in reciprocal cortico-thalamic connectivity. However, analysis of broader cortical phenotypes in this model has yet to be performed. Here, we addressed this, revealing that dorsal telencephalon-specific ablation of Setd2 results in decreased structural volumes across the entire adult brain, particularly within the hippocampus. Moreover, while homozygous Setd2-deficient brains exhibited apparently normal axonal integrity within the corpus callosum, axonal connections arising from the hippocampus were significantly impacted. Furthermore, whole brain structural connectivity was significantly altered in the absence of Setd2. Finally, we revealed structural, morphological and cellular changes within the hippocampal dentate gyrus of mutant mice. Collectively, these findings demonstrate a key role for SETD2 function in the development of the adult brain.