An innate pathogen sensing strategy involving ubiquitination of bacterial surface proteins.

Sensing of pathogens by ubiquitination is a critical arm of cellular immunity. However, universal ubiquitination targets on microbes remain unidentified. Here, using in vitro, ex vivo, and in vivo studies, we identify the first protein-based ubiquitination substrates on phylogenetically diverse bacteria by unveiling a strategy that uses recognition of degron-like motifs. Such motifs form a new class of intra-cytosolic pathogen-associated molecular patterns (PAMPs). Their incorporation enabled recognition of nonubiquitin targets by host ubiquitin ligases. We find that SCFFBW7 E3 ligase, supported by the regulatory kinase, glycogen synthase kinase 3β, is crucial for effective pathogen detection and clearance. This provides a mechanistic explanation for enhanced risk of infections in patients with chronic lymphocytic leukemia bearing mutations in F-box and WD repeat domain containing 7 protein. We conclude that exploitation of this generic pathogen sensing strategy allows conservation of host resources and boosts antimicrobial immunity

Segmentering av cancerepitel utifrån kärnmorfologi med djupinlärning

Bladder cancer (BCa) is the fourth most commonly diagnosed cancers in men and the eighth most common in women. It is an abnormal growth of tissues which develops in the bladder lining. Histological analysis of bladder tissue facilities diagnosis as well as it serves as an important tool for research. To bet- ter understand the molecular profile of bladder cancer and to detect predictive and prognostic features, microscopy methods, such as immunofluorescence (IF), are used to investigate the characteristics of bladder cancer tissue. For this project, a new method is proposed to segment cancer epithelial us- ing nuclei morphology captured with IF staining. The method is implemented using deep learning algorithms and performance achieved is compared with the literature. The dataset is stained for nuclei (DAPI) and a marker for cancer epithelial (panEPI) which was used to create the ground truth. Three popu- lar Convolutional Neural Network (CNN) namely U-Net, Residual U-Net and VGG16 were implemented to perform the segmentation task on the tissue mi- croarray dataset. In addition, a transfer learning approach was tested with the VGG16 network that was pre-trained with ImageNet dataset. Further, the performance from the three networks were compared using 3fold cross-validation. The dice accuracies achieved were 83.32% for U-Net, 88.05% for Residual U-Net and 82.73% for VGG16. These findings suggest that segmentation of cancerous tissue regions, using only the nuclear morphol- ogy, is feasible with high accuracy. Computer vision methods better utilizing nuclear morphology captured by the nuclear stain, are promising approaches to digitally augment the conventional IF marker panels, and therefore offer im- proved resolution of the molecular characteristics for research settings

Segmentering av cancerepitel utifrån kärnmorfologi med djupinlärning

Bladder cancer (BCa) is the fourth most commonly diagnosed cancers in men and the eighth most common in women. It is an abnormal growth of tissues which develops in the bladder lining. Histological analysis of bladder tissue facilities diagnosis as well as it serves as an important tool for research. To bet- ter understand the molecular profile of bladder cancer and to detect predictive and prognostic features, microscopy methods, such as immunofluorescence (IF), are used to investigate the characteristics of bladder cancer tissue. For this project, a new method is proposed to segment cancer epithelial us- ing nuclei morphology captured with IF staining. The method is implemented using deep learning algorithms and performance achieved is compared with the literature. The dataset is stained for nuclei (DAPI) and a marker for cancer epithelial (panEPI) which was used to create the ground truth. Three popu- lar Convolutional Neural Network (CNN) namely U-Net, Residual U-Net and VGG16 were implemented to perform the segmentation task on the tissue mi- croarray dataset. In addition, a transfer learning approach was tested with the VGG16 network that was pre-trained with ImageNet dataset. Further, the performance from the three networks were compared using 3fold cross-validation. The dice accuracies achieved were 83.32% for U-Net, 88.05% for Residual U-Net and 82.73% for VGG16. These findings suggest that segmentation of cancerous tissue regions, using only the nuclear morphol- ogy, is feasible with high accuracy. Computer vision methods better utilizing nuclear morphology captured by the nuclear stain, are promising approaches to digitally augment the conventional IF marker panels, and therefore offer im- proved resolution of the molecular characteristics for research settings

Segmentering av cancerepitel utifrån kärnmorfologi med djupinlärning

Bladder cancer (BCa) is the fourth most commonly diagnosed cancers in men and the eighth most common in women. It is an abnormal growth of tissues which develops in the bladder lining. Histological analysis of bladder tissue facilities diagnosis as well as it serves as an important tool for research. To bet- ter understand the molecular profile of bladder cancer and to detect predictive and prognostic features, microscopy methods, such as immunofluorescence (IF), are used to investigate the characteristics of bladder cancer tissue. For this project, a new method is proposed to segment cancer epithelial us- ing nuclei morphology captured with IF staining. The method is implemented using deep learning algorithms and performance achieved is compared with the literature. The dataset is stained for nuclei (DAPI) and a marker for cancer epithelial (panEPI) which was used to create the ground truth. Three popu- lar Convolutional Neural Network (CNN) namely U-Net, Residual U-Net and VGG16 were implemented to perform the segmentation task on the tissue mi- croarray dataset. In addition, a transfer learning approach was tested with the VGG16 network that was pre-trained with ImageNet dataset. Further, the performance from the three networks were compared using 3fold cross-validation. The dice accuracies achieved were 83.32% for U-Net, 88.05% for Residual U-Net and 82.73% for VGG16. These findings suggest that segmentation of cancerous tissue regions, using only the nuclear morphol- ogy, is feasible with high accuracy. Computer vision methods better utilizing nuclear morphology captured by the nuclear stain, are promising approaches to digitally augment the conventional IF marker panels, and therefore offer im- proved resolution of the molecular characteristics for research settings