Dataset Information

Integrative and quantitative view of the CtrA regulatory network in a stalked budding bacterium.

ABSTRACT: The Alphaproteobacteria show a remarkable diversity of cell cycle-dependent developmental patterns, which are governed by the conserved CtrA pathway. Its central component CtrA is a DNA-binding response regulator that is controlled by a complex two-component signaling network, mediating distinct transcriptional programs in the two offspring. The CtrA pathway has been studied intensively and was shown to consist of an upstream part that reads out the developmental state of the cell and a downstream part that integrates the upstream signals and mediates CtrA phosphorylation. However, the role of this circuitry in bacterial diversification remains incompletely understood. We have therefore investigated CtrA regulation in the morphologically complex stalked budding alphaproteobacterium Hyphomonas neptunium. Compared to relatives dividing by binary fission, H. neptunium shows distinct changes in the role and regulation of various pathway components. Most notably, the response regulator DivK, which normally links the upstream and downstream parts of the CtrA pathway, is dispensable, while downstream components such as the pseudokinase DivL, the histidine kinase CckA, the phosphotransferase ChpT and CtrA are essential. Moreover, CckA is compartmentalized to the nascent bud without forming distinct polar complexes and CtrA is not regulated at the level of protein abundance. We show that the downstream pathway controls critical functions such as replication initiation, cell division and motility. Quantification of the signal flow through different nodes of the regulatory cascade revealed that the CtrA pathway is a leaky pipeline and must involve thus-far unidentified factors. Collectively, the quantitative system-level analysis of CtrA regulation in H. neptunium points to a considerable evolutionary plasticity of cell cycle regulation in alphaproteobacteria and leads to hypotheses that may also hold in well-established model organisms such as Caulobacter crescentus.

SUBMITTER: Leicht O

PROVIDER: S-EPMC7200025 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Integrative and quantitative view of the CtrA regulatory network in a stalked budding bacterium.

Leicht Oliver O van Teeseling Muriel C F MCF Panis Gaël G Reif Celine C Wendt Heiko H Viollier Patrick H PH Thanbichler Martin M

PLoS genetics 20200423 4

The Alphaproteobacteria show a remarkable diversity of cell cycle-dependent developmental patterns, which are governed by the conserved CtrA pathway. Its central component CtrA is a DNA-binding response regulator that is controlled by a complex two-component signaling network, mediating distinct transcriptional programs in the two offspring. The CtrA pathway has been studied intensively and was shown to consist of an upstream part that reads out the developmental state of the cell and a downstre ...[more]

PMID: 32324740

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Project description:Alphaproteobacteria stand out for their complex cell cycles, which are often regulated by the DivJ/PleC-DivK-DivL-CckA-ChpT-CtrA pathway. DivJ and PleC set up the polarity of the cell, thereby eventually leading to differential activation of the DNA-binding response regulator CtrA in the two nascent daughter cells. CtrA regulates replication and transcription of many genes, thereby ensuring that processes such as motility and cell division take place at the appropriate cell cycle stage. The cell cycle of the stalked budding alphaproteobacterium Hyphomonas neptunium culminates in an asymmetric cell division at the stalk-bud junction. Here, we investigate the role of the pathway from DivJ and PleC down to CtrA in this recently established model organism. Even though DivJ and PleC are localized to opposite poles, suggesting they are involved in polarity establishment inH. neptunium, DivJ, PleC and the other components of the upstream pathway (DivK and PleD) are not essential for cell cycle regulation. In contrast, the downstream part of the pathway starting from DivL is essential and involved in the regulation of important functions such as replication inhibition, cell division and motility, as shown by the identification of the (direct) regulon of CtrA. The overlap between the regulons of DivJ and PleC, DivK and CtrA is only partial, demonstrating that additional factors feeding into the pathway must be present in H. neptunium. Furthermore, unlike in other alphaproteobacteria, the regulation of CtrA throughout the cell cycle does not take place at the level of CtrA abundance in H. neptunium. All in all, the DivL-CckA-ChpT-CtrA pathway plays an essential role in the regulation of the complicated cell cycle ofH. neptunium, but several proteins feeding into CtrA remain undiscovered. The in-depth analysis of CtrA regulation in this stalked budding organism leads to hypotheses that might also hold in well-established model organisms such as Caulobacter crescentus.

Project description:Summary Decreasing projection views to a lower X-ray radiation dose usually leads to severe streak artifacts. To improve image quality from sparse-view data, a multi-domain integrative Swin transformer network (MIST-net) was developed and is reported in this article. First, MIST-net incorporated lavish domain features from data, residual data, image, and residual image using flexible network architectures, where a residual data and residual image sub-network was considered as a data consistency module to eliminate interpolation and reconstruction errors. Second, a trainable edge enhancement filter was incorporated to detect and protect image edges. Third, a high-quality reconstruction Swin transformer (i.e., Recformer) was designed to capture image global features. The experimental results on numerical and real cardiac clinical datasets with 48 views demonstrated that our proposed MIST-net provided better image quality with more small features and sharp edges than other competitors. Highlights • A multi-domain integrative Swin transformer was proposed for spare-data imaging• A trainable image edge enhancement filter recovers sharp image edges and features• A modified vision transformer first demonstrates its great potential in tomography• Patient clinical cardiac and numerical data demonstrate our MIST power The bigger picture Decreasing projection views to a lower X-ray radiation dose usually leads to severe streak artifacts. To improve reconstructed image quality from sparse-view data, we develop a multi-domain integrative Swin transformer (MIST) network in this study. The proposed MIST-net incorporates lavish domain features from data, residual data, image, and residual image using flexible network architectures, which help deeply mine the data and image features. To detect image features and protect image edges, the trainable edge enhancement filter is further incorporated to the network for improving encode-decode ability. A high-quality reconstruction transformer was designed to improve the ability of global feature extraction. Our results from both simulation and real cardiac data demonstrated the great potential of MIST. A multi-domain integrative Swin transformer network (MIST-net) demonstrates feasibility, advantages, and great potential in sparse-view tomographic reconstruction. MIST-net mainly integrates data, image, residual data, and residual image domain information into a unified model with a trainable edge enhancement filter and advanced transformer AI technique to realize ultra-sparse-data (48 views) high-fidelity imaging.

Dataset Information

Integrative and quantitative view of the CtrA regulatory network in a stalked budding bacterium.

Publications

Integrative and quantitative view of the CtrA regulatory network in a stalked budding bacterium.

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