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Mutational signatures of single-base substitutions (SBSs) characterize somatic mutation processes which contribute to cancer development and progression. However, current mutational signatures do not distinguish the two independent steps that generate SBSs: the initial DNA damage followed by erroneous repair. To address this modelling gap we developed DAMUTA, a hierarchical Bayesian probabilistic model that infers separate signatures for each process, and captures their sample-specific...

RUVBL1 and RUVBL2 proteins assemble into a heterohexameric ring and are essential for DNA repair in prokaryotes and chromatin homeostasis in eukaryotes. These proteins function as potential chaperones and ATPases. While most studies on eukaryotic RUVBL1/2 proteins have focused on human and yeast orthologs, they have revealed notable differences in conformational dynamics, protein interactions, and ATPase activity between these species. By investigating orthologs in other eukaryotic organisms,...

CONCLUSION: Ethiopian nurse-physician mentorship pairs supporting mentee hospitals in standardizing assessments of respiratory distress and optimizing the use of CPAP increased the number of preterm infants treated with CPAP. Significant reduction in preterm mortality postintervention is encouraging as CPAP use continues to scale up globally.

Prostate cancer cell lines are particularly clinically homogenous, mostly representing metastatic states rather than localized disease. While there has been significant work in the development of additional models, few have been created without oncogenic transformation. We derived a primary prostate cancer cell line from a patient with localized Gleason 7 prostate cancer-designated CaB34-which spontaneously immortalized. We leveraged CaB34 to generate a paired radioresistant subline, CaB34-CF,...

Diverse small RNA pathways, composed of Argonaute effector proteins and their bound small RNA molecules, define critical systems for regulating gene expression in all domains of life. Some small RNA pathways have experienced significant evolutionary change across metazoans, including gains of novel Argonaute genes and losses of entire pathways. Differences in Argonaute functional complement among species therefore profoundly influence the available repertoire of mechanisms for gene regulation....

Cardiac fibrosis during Duchenne muscular dystrophy (DMD) arises from cellular damage and inflammation and is associated with metabolic dysfunction. The extent to which these relationships develop across all 4 cardiac chambers, particularly during early-stage disease, remains unknown. We discovered that very young D2.mdx mice exhibit fibrosis exclusively in the right ventricle (RV) and left atrium. Concurrent myocardial disorganization in the RV was related to a highly specific inflammatory...

CONCLUSIONS: The workshop provided a unique opportunity for early-career researchers to expand their network, and for all participants to discuss new or improved approaches to advance the field, including international consortia and data sharing. The highlights and outcomes from this OA epigenetics workshop are described in this report.

Transposable elements (TEs) provide a source of transcription factor (TF) binding sites that can rewire gene regulatory networks. NF-kB is an evolutionarily conserved TF complex primarily involved in innate immunity and inflammation. The extent to which TEs have contributed to NF-kB responses during mammalian evolution is not well established. Here, we performed a multi-species analysis of TEs bound by the NF-kB subunit RELA in response to the proinflammatory cytokine TNF. By comparing RELA...

CONCLUSIONS: These data yield insights into the role of PTCHD1 in neurodevelopment and neurotransmission and suggest a neuropathological mechanism for missense variants. These findings provide a platform for diagnostic assay and VUS interpretation, allowing for clinical reclassification of these variants.

Electrochemical nitrate reduction reaction (NO(3)RR) is a promising approach to simultaneously realize pollutant removal and ammonia generation. However, this process involves the transfer of eight electrons and nine protons along with multiple by-products, resulting in a significant challenge for achieving high ammonia yield and selectivity. Herein, we introduced bimetallic covalent organic frameworks catalysts with Cu and Co active sites to achieve a two-step tandem reaction, avoiding...

The recent Kunming-Montreal Global Biodiversity Framework (GBF) sets ambitious goals but no clear pathway for how zero loss of important biodiversity areas and halting human-induced extinction of threatened species will be achieved. We assembled a multi-taxa tracking dataset (11 million geopositions from 15,845 tracked individuals across 121 species) to provide a global assessment of space use of highly mobile marine megafauna, showing that 63% of the area that they cover is used 80% of the time...

CONCLUSIONS: We highlight the importance of examining heterogeneity in autism and ADHD and demonstrate that population modelling is a useful tool to study subgrouping in autism and ADHD. We identified subgroups with distinct patterns of alterations relative to controls but note that these results rely heavily on the algorithm used and encourage detailed reporting of methods and features used in future studies.

Pyropia yezoensis, a key economic marine crop in Asia, serves as a model for red seaweed research. Previously, we determined that histone acetylation plays essential roles in the response to abiotic stresses and the formation of asexual spores in P. yezoensis. However, the reader proteins of acetylated histones remain to be identified. In this study, we characterized the gene encoding a YEATS domain-containing protein (PyYEATS) in P. yezoensis. The PyYEATS protein, mainly localized in nuclei...

CONCLUSIONS AND RELEVANCE: In this prognostic study, a proactive, label-agnostic monitoring pipeline detected harmful data shifts for a clinical AI system predicting in-hospital mortality. Transfer learning and drift-triggered continual learning strategies mitigated performance degradation, maintaining model performance across health care settings. These findings suggest that the approach used here may ensure the robust and equitable deployment of clinical AI models. Future research should...

Major Depressive Disorder (MDD) demonstrates heterogeneous symptom profiles and a high relapse risk. Understanding how symptom interactions relate to relapse in MDD may enhance maintenance strategies. We thus investigated how connectivity in depressive symptom networks relates to relapse in MDD. We analyzed longitudinal data from 87 patients with remitted MDD who were followed for an average of 12 months. Patient-level symptom networks were estimated using multilevel graphical vector...

We outline the development of the Health Data Nexus, a data platform that enables data storage and access management with a cloud-based computational environment. We describe the importance of this secure platform in an evolving public-sector research landscape that utilizes significant quantities of data, particularly clinical data acquired from health systems, as well as the importance of providing meaningful benefits for three targeted user groups: data providers, researchers, and educators....