Highly efficient optogenetic cell ablation in C. elegans using membrane-targeted miniSOG.

The genetically encoded photosensitizer miniSOG (mini Singlet Oxygen Generator) can be used to kill cells in C. elegans. miniSOG generates the reactive oxygen species (ROS) singlet oxygen after illumination with blue light. Illumination of neurons expressing miniSOG targeted to the outer mitochondrial membrane (mito-miniSOG) causes neuronal death. To enhance miniSOG's efficiency as an ablation tool in multiple cell types we tested alternative targeting signals. We find that membrane targeted miniSOG allows highly efficient cell killing. When combined with a point mutation that increases miniSOG's ROS generation, membrane targeted miniSOG can ablate neurons in less than one tenth the time of mito-miniSOG. We extend the miniSOG ablation technique to non-neuronal tissues, revealing an essential role for the epidermis in locomotion. These improvements expand the utility and throughput of optogenetic cell ablation in C. elegans

Wounding triggers MIRO-1 dependent mitochondrial fragmentation that accelerates epidermal wound closure through oxidative signaling.

Organisms respond to tissue damage through the upregulation of protective responses which restore tissue structure and metabolic function. Mitochondria are key sources of intracellular oxidative metabolic signals that maintain cellular homeostasis. Here we report that tissue and cellular wounding triggers rapid and reversible mitochondrial fragmentation. Elevated mitochondrial fragmentation either in fzo-1 fusion-defective mutants or after acute drug treatment accelerates actin-based wound closure. Wounding triggered mitochondrial fragmentation is independent of the GTPase DRP-1 but acts via the mitochondrial Rho GTPase MIRO-1 and cytosolic Ca2+. The fragmented mitochondria and accelerated wound closure of fzo-1 mutants are dependent on MIRO-1 function. Genetic and transcriptomic analyzes show that enhanced mitochondrial fragmentation accelerates wound closure via the upregulation of mtROS and Cytochrome P450. Our results reveal how mitochondrial dynamics respond to cellular and tissue injury and promote tissue repair

A Gαq-Ca2+ Signaling Pathway Promotes Actin-Mediated Epidermal Wound Closure in C. elegans

SummaryBackgroundRepair of skin wounds is essential for animals to survive in a harsh environment, yet the signaling pathways initiating wound repair in vivo remain little understood. In Caenorhabditis elegans, a p38 mitogen-activated protein kinase (MAPK) cascade promotes innate immune responses to wounding but is not required for other aspects of wound healing. We therefore set out to identify additional wound response pathways in C. elegans epidermis.ResultsWe show here that wounding the adult C. elegans skin triggers a rapid and sustained rise in epidermal Ca2+ that is critical for survival after wounding. The wound-triggered rise in Ca2+ requires the epidermal transient receptor potential channel, melastatin family (TRPM) channel GTL-2 and IP3R-stimulated release from internal stores. We identify an epidermal signal transduction pathway that includes the Gαq EGL-30 and its effector PLCβ EGL-8. Loss of function in this pathway impairs survival after wounding. The Gαq-Ca2+ pathway is not required for known innate immune responses to wounding but instead promotes actin-dependent wound closure. Wound closure requires the Cdc42 small GTPase and Arp2/3-dependent actin polymerization and is negatively regulated by Rho and nonmuscle myosin. Finally, we show that the death-associated protein kinase DAPK-1 acts as a negative regulator of wound closure.ConclusionsSkin wounding in C. elegans triggers a Ca2+-dependent signaling cascade that promotes wound closure, in parallel to the innate immune response to damage. Wound closure requires actin polymerization and is negatively regulated by nonmuscle myosin

Fine-Grained Extraction of Road Networks via Joint Learning of Connectivity and Segmentation

Road network extraction from satellite images is widely applicated in intelligent traffic management and autonomous driving fields. The high-resolution remote sensing images contain complex road areas and distracted background, which make it a challenge for road extraction. In this study, we present a stacked multitask network for end-to-end segmenting roads while preserving connectivity correctness. In the network, a global-aware module is introduced to enhance pixel-level road feature representation and eliminate background distraction from overhead images; a road-direction-related connectivity task is added to ensure that the network preserves the graph-level relationships of the road segments. We also develop a stacked multihead structure to jointly learn and effectively utilize the mutual information between connectivity learning and segmentation learning. We evaluate the performance of the proposed network on three public remote sensing datasets. The experimental results demonstrate that the network outperforms the state-of-the-art methods in terms of road segmentation accuracy and connectivity maintenance

Association between serum uric acid and colorectal cancer risk in European population: a two-sample Mendelian randomization study

ObjectivesThis study aimed to explore the potential causal associations between serum uric acid (SUA) and the risk of colorectal cancer, colon cancer and rectal cancer.MethodsTwenty-six SUA-related single nucleotide polymorphisms which were identified by a large meta-analysis of genome-wide association studies (GWASs) were used as instrumental variables in the two-sample Mendelian randomization (MR) study. Meta-analyses were used to synthesize the results of multiple GWASs which were extracted from the MRC Integrative Epidemiology Unit GWAS database for each type of cancer. The inverse variance weighted (IVW) method was used as the primary MR method to analyze the association between SUA and colorectal cancer risk. Several sensitivity analyses were performed to test the robustness of results.ResultsThe IVW method showed that there were no causal relationships between SUA and the risk of colorectal cancer [odds ratio (OR): 1.0015; 95% confidence interval (CI): 0.9975–1.0056] and colon cancer (OR: 1.0015; 95% CI: 0.9974–1.0055). The SUA levels were negative correlated with rectal cancer risk (OR: 0.9984; 95% CI: 0.9971–0.9998). The similar results were observed in both males (OR: 0.9987; 95% CI: 0.9975–0.9998) and females (OR: 0.9985; 95% CI: 0.9971–0.9999). The sensitivity analyses suggested no evidence of heterogeneity or horizontal pleiotropy. The leave-one-out analyses showed that one SNP (rs1471633) significantly drove the causal effect of SUA on rectal cancer risk. The MR-Egger regression and weighted median both showed that there were no causal relationships between SUA and the risk of colorectal cancer and its subtypes.ConclusionOverall, there was no linear causal association between SUA and the risk of colorectal cancer. However, further research is needed to investigate the role of higher SUA levels such as hyperuricemia or gout in the occurrence of colorectal cancer

Development and validation of a three-dimensional deep learning-based system for assessing bowel preparation on colonoscopy video

BackgroundThe performance of existing image-based training models in evaluating bowel preparation on colonoscopy videos was relatively low, and only a few models used external data to prove their generalization. Therefore, this study attempted to develop a more precise and stable AI system for assessing bowel preparation of colonoscopy video.MethodsWe proposed a system named ViENDO to assess the bowel preparation quality, including two CNNs. First, Information-Net was used to identify and filter out colonoscopy video frames unsuitable for Boston bowel preparation scale (BBPS) scoring. Second, BBPS-Net was trained and tested with 5,566 suitable short video clips through three-dimensional (3D) convolutional neural network (CNN) technology to detect BBPS-based insufficient bowel preparation. Then, ViENDO was applied to complete withdrawal colonoscopy videos from multiple centers to predict BBPS segment scores in clinical settings. We also conducted a human-machine contest to compare its performance with endoscopists.ResultsIn video clips, BBPS-Net for determining inadequate bowel preparation generated an area under the curve of up to 0.98 and accuracy of 95.2%. When applied to full-length withdrawal colonoscopy videos, ViENDO assessed bowel cleanliness with an accuracy of 93.8% in the internal test set and 91.7% in the external dataset. The human-machine contest demonstrated that the accuracy of ViENDO was slightly superior compared to most endoscopists, though no statistical significance was found.ConclusionThe 3D-CNN-based AI model showed good performance in evaluating full-length bowel preparation on colonoscopy video. It has the potential as a substitute for endoscopists to provide BBPS-based assessments during daily clinical practice

Maternal xNorrin, a Canonical Wnt Signaling Agonist and TGF-β Antagonist, Controls Early Neuroectoderm Specification in Xenopus

Xenopus maternal Norrin, which activates Wnt signaling but inhibits TGF-β family molecules, is essential for neuroectoderm formation. Loss of TGF-β inhibition in Norrin may contribute to the development of Norrie disease