Epigenetic control of Topoisomerase 1 activity presents a cancer vulnerability.

DNA transactions introduce torsional constraints that pose an inherent risk to genome integrity. While topoisomerase 1 (TOP1) activity is essential for removing DNA supercoiling, aberrant stabilization of TOP1:DNA cleavage complexes (TOP1ccs) can result in cytotoxic DNA lesions. What protects genomic hot spots of topological stress from aberrant TOP1 activity remains unknown.

Coinhibition of topoisomerase 1 and BRD4-mediated pause release selectively kills pancreatic cancer via readthrough transcription.

Pancreatic carcinoma lacks effective therapeutic strategies resulting in poor prognosis. Transcriptional dysregulation due to alterations in KRAS and MYC affects initiation, development, and survival of this tumor type. Using patient-derived xenografts of KRAS- and MYC-driven pancreatic carcinoma, we show that coinhibition of topoisomerase 1 (TOP1) and bromodomain-containing protein 4 (BRD4) synergistically induces tumor regression by targeting promoter pause release.

Disruptions in modular structure and network integration of language-related network predict language performance in temporal lobe epilepsy: Evidence from graph-based analysis.

Objective: Temporal lobe epilepsy (TLE) is a network disorder that alters the total organization of the language-related network. Task-based functional magnetic resonance imaging (fMRI) aimed at functional connectivity is a direct method to investigate how the network is reorganized. However, such studies are scarce and represented mostly by the resting-state analysis of the individual connections between regions.

Experimental Studies of the Liposomal Form of Lytic Mycobacteriophage D29 for the Treatment of Tuberculosis Infection.

We have studied the antimycobacterial efficacy of the liposomal preparation of mycobacteriophage D29 on models of tuberculous granuloma in vitro and in the experiment on laboratory mice of the relatively resistant strain C57BL/6, infected with the virulent strain of H37Rv. We have shown the preparation of liposomal preparation of the lytic mycobacteriophages and its characteristics. The experiments showed a significant lytic effect of the liposomal form of mycobacteriophage D29 both on the model of tuberculous granuloma formed by human blood mononuclear cells in vitro, which is formed in the presence of and on the model of tuberculous infection in C57BL/6 mice.

Source-Storage-Load Coordinated Master-Slave Control Strategy for Islanded Microgrid Considering Load Disturbance and Communication Interruption.

When there is a sudden load disturbance in an islanded microgrid, the peer-to-peer control model requires the energy resource to maintain a margin of generation, resulting in a relatively limited regulation range, that is, voltage/frequency sometimes requires additional control to maintain stability. A "source-storage-load" coordinated master-slave control strategy is proposed in this study to address the aforementioned issues. The system voltage and frequency will be stable as long as the output frequency and voltage of the master resource are stable.