Xiaolan Zhu

Most information retrieval systems on the Internet rely primarily on similarity ranking algorithms based solely on term frequency statistics. Information quality is usually ignored. This leads to the problem that documents are retrieved without regard to their quality. We present an approach that combines similarity-based similarity ranking with quality ranking in centralized and distributed search environments. Six quality metrics, including the currency, availability, information-to-noise ratio, authority, popularity, and cohesiveness, were investigated. Search effectiveness was significantly improved when the currency, availability, information-to-noise ratio and page cohesiveness metrics were incorporated in centralized search. The improvement seen when the availability, information-to- noise ratio, popularity, and cohesiveness metrics were incorporated in site selection was also significant. Finally, incorporating the popularity metric in information fusion resulted in a significant improvement. In summary, the results show that incorporating quality metrics can generally improve search effectiveness in both centralized and distributed search environments.

Abstract Recruitment of DNA repair proteins to DNA damage sites is a critical step for DNA repair. Post-translational modifications of proteins at DNA damage sites serve as DNA damage codes to recruit specific DNA repair factors. Here, we show that mRNA is locally modified by m 5 C at sites of DNA damage. The RNA methyltransferase TRDMT1 is recruited to DNA damage sites to promote m 5 C induction. Loss of TRDMT1 compromises homologous recombination (HR) and increases cellular sensitivity to DNA double-strand breaks (DSBs). In the absence of TRDMT1, RAD51 and RAD52 fail to localize to sites of reactive oxygen species (ROS)-induced DNA damage. In vitro, RAD52 displays an increased affinity for DNA:RNA hybrids containing m 5 C-modified RNA. Loss of TRDMT1 in cancer cells confers sensitivity to PARP inhibitors in vitro and in vivo. These results reveal an unexpected TRDMT1-m 5 C axis that promotes HR, suggesting that post-transcriptional modifications of RNA can also serve as DNA damage codes to regulate DNA repair.

BACKGROUND: Neuroinflammation is an important component mechanism in the development of depression. Exosomal transfer of MDD-associated microRNAs (miRNAs) from neurons to microglia might exacerbate neuronal cell inflammatory injury. RESULTS: By sequence identification, we found significantly higher miR-9-5p expression levels in serum exosomes from MDD patients than healthy control (HC) subjects. Then, in cultured cell model, we observed that BV2 microglial cells internalized PC12 neuron cell-derived exosomes while successfully transferring miR-9-5p. MiR-9-5p promoted M1 polarization in microglia and led to over releasing of proinflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), which exacerbated neurological damage. Furthermore, we identified suppressor of cytokine signaling 2 (SOCS2) as a direct target of miR-9-5p. Overexpression of miR-9-5p suppressed SOCS2 expression and reactivated SOCS2-repressed Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathways. Consistently, we confirmed that adeno-associated virus (AAV)-mediated overexpression of miR-9-5p polarized microglia toward the M1 phenotype and exacerbated depressive symptoms in chronic unpredictable mild stress (CUMS) mouse mode. CONCLUSION: MiR-9-5p was transferred from neurons to microglia in an exosomal way, leading to M1 polarization of microglia and further neuronal injury. The expression and secretion of miR-9-5p might be novel therapeutic targets for MDD.