RTCB deficiency triggers colitis in mice by influencing the NF-κB and Wnt/ß-catenin signaling pathways.

RNA terminal phosphorylase B (RTCB) has been shown to play a significant role in multiple physiological processes. However, the specific role of RTCB in the mouse colon remains unclear. In this study, we employ a conditional knockout mouse model to investigate the effects of RTCB depletion on the colon and the potential molecular mechanisms. We assess the efficiency and phenotype of Rtcb knockout using PCR, western blot analysis, histological staining, and immunohistochemistry. Compared with the control mice, the Rtcb-knockout mice exhibit compromised colonic barrier integrity and prominent inflammatory cell infiltration. In the colonic tissues of Rtcb-knockout mice, the protein levels of TNF-α, IL-8, and p-p65 are increased, whereas the levels of IKKß and IκBα are decreased. Moreover, the level of GSK3ß is increased, whereas the levels of Wnt3a, ß-catenin, and LGR5 are decreased. Collectively, our findings unveil a close association between RTCB and colonic tissue homeostasis and demonstrate that RTCB deficiency can lead to dysregulation of both the NF-κB and Wnt/ß-catenin signaling pathways in colonic cells.

Transcription-replication interactions reveal bacterial genome regulation.

Organisms determine the transcription rates of thousands of genes through a few modes of regulation that recur across the genome1. In bacteria, the relationship between the regulatory architecture of a gene and its expression is well understood for individual model gene circuits2,3. However, a broader perspective of these dynamics at the genome scale is lacking, in part because bacterial transcriptomics has hitherto captured only a static snapshot of expression averaged across millions of cells4. As a result, the full diversity of gene expression dynamics and their relation to regulatory architecture remains unknown. Here we present a novel genome-wide classification of regulatory modes based on the transcriptional response of each gene to its own replication, which we term the transcription-replication interaction profile (TRIP). Analysing single-bacterium RNA-sequencing data, we found that the response to the universal perturbation of chromosomal replication integrates biological regulatory factors with biophysical molecular events on the chromosome to reveal the local regulatory context of a gene. Whereas the TRIPs of many genes conform to a gene dosage-dependent pattern, others diverge in distinct ways, and this is shaped by factors such as intra-operon position and repression state. By revealing the underlying mechanistic drivers of gene expression heterogeneity, this work provides a quantitative, biophysical framework for modelling replication-dependent expression dynamics.

Cerium oxide nanoparticles modulating the Parkinson's disease conditions: From the alpha synuclein structural point of view and antioxidant properties of cerium oxide nanoparticles.

Parkinson's and Alzheimer's disease is the main cause of dementia, which is associated with the progressive deterioration of the intelligence and senses. Free radicals are created during oxidative stress in cells, which are considered one of the destructive factors in neurodegenerative diseases. In this study, the antifibrillar and antioxidant properties of cerium oxide nanoparticles (CeO2 NPs) were investigated experimentally and theoretically. The CeO2 NPs were synthesized and analyzed to reveal the physicochemical and biological properties. The results showed that the CeO2 NPs have unique properties with potent antioxidant activities. The experimental and computational studies showed that the CeO2 NPs interact with the active site of Alpha-synuclein. The existence of hydrogen bonding between O atoms of CeO2 NPs and N-H of adjacent acid amines and the equilibrium distances were confirmed by 1.751 (Leu100), 1.786 (Gln99) and 2.213 Å (Lys97). The minimum free energy binding of L-DOPA drug (as positive control) and CeO2 NPs were negative, resulting interaction between compounds and protein. As a result, these compounds inhibited Alpha-synuclein protein aggregation. In addition, that CeO2 NPs strongly binds with receptor by relative binding energy as compared with L-DOPA drug. These findings revealed that CeO2 NPs prevent Alpha-synuclein fibrillation and can be applied as nano-drug against the Parkinson's disease.

Transcription-replication interactions reveal principles of bacterial genome regulation.

Organisms determine the transcription rates of thousands of genes through a few modes of regulation that recur across the genome1. These modes interact with a changing cellular environment to yield highly dynamic expression patterns2. In bacteria, the relationship between a gene's regulatory architecture and its expression is well understood for individual model gene circuits3,4. However, a broader perspective of these dynamics at the genome-scale is lacking, in part because bacterial transcriptomics have hitherto captured only a static snapshot of expression averaged across millions of cells5. As a result, the full diversity of gene expression dynamics and their relation to regulatory architecture remains unknown. Here we present a novel genome-wide classification of regulatory modes based on each gene's transcriptional response to its own replication, which we term the Transcription-Replication Interaction Profile (TRIP). We found that the response to the universal perturbation of chromosomal replication integrates biological regulatory factors with biophysical molecular events on the chromosome to reveal a gene's local regulatory context. While the TRIPs of many genes conform to a gene dosage-dependent pattern, others diverge in distinct ways, including altered timing or amplitude of expression, and this is shaped by factors such as intra-operon position, repression state, or presence on mobile genetic elements. Our transcriptome analysis also simultaneously captures global properties, such as the rates of replication and transcription, as well as the nestedness of replication patterns. This work challenges previous notions of the drivers of expression heterogeneity within a population of cells, and unearths a previously unseen world of gene transcription dynamics.