Mechanistically, the deletion of Rap1A led to elevated eNOS phosphorylation both at the inhibitory, T495, and the activating Ser1177 residues. These findings indicate that the two Rap1 isoforms act via distinct signaling pathways while Rap1B directly positively regulates eNOS activation, Rap1A prevents negative regulation of eNOS. Notably, the combined deficiency of Rap1A and Rap1B has a severe effect on eNOS activity and NO release with an in vivo impact on endothelial function and vascular homeostasis.White matter damage caused by cerebral hypoperfusion is a major hallmark of subcortical ischemic vascular dementia (SIVD), which is the most common subtype of vascular cognitive impairment and dementia (VCID) syndrome. In an aging society, the number of SIVD patients is expected to increase; however, effective therapies have yet to be developed. To understand the pathological mechanisms, we analyzed the profiles of the cells of the corpus callosum after cerebral hypoperfusion in a preclinical SIVD model. We prepared cerebral hypoperfused mice by subjecting 2-month old male C57BL/6J mice to bilateral carotid artery stenosis (BCAS) operation. BCAS-hypoperfusion mice exhibited cognitive deficits at 4 weeks after cerebral hypoperfusion, assessed by novel object recognition test. RNA samples from the corpus callosum region of sham- or BCAS-operated mice were then processed using RNA sequencing. A gene set enrichment analysis using differentially expressed genes between sham and BCAS-operated mice showed activation of oligodendrogenesis pathways along with angiogenic responses. This database of transcriptomic profiles of BCAS-hypoperfusion mice will be useful for future studies to find a therapeutic target for SIVD.Cyclin Y (CCNY) is a novel cyclin and highly conserved in metazoan species. Previous studies from our and other laboratory indicate that CCNY play a crucial role in tumor progression. There are two CCNY isoform which has different subcellular distributions, with cytoplasmic isoform (CCNYc) and membrane distribution isoform (CCNYm). However, the expression and function of CCNY isoforms is still unclear. We firstly found CCNYc was expressed in natural lung cancer tissue and cells through the subcellular distribution. Co-IP and immunofluorescence showed that both CCNYm and CCNYc could interact with PFTK1. Further studies illustrated that CCNYc but not CCNYm enhanced cell migration and invasion activity both in vivo and vitro. The function of CCNYc could be inhibited by suppression of PFTK1 expression. In addition, our data indicated that tropomyosin 4 (TPM4), a kind of actin-binding proteins, was down-regulated by suppression of CCNY. F-actin assembly could be controlled by CCNYc as well as PFTK1 and TPM4.  https://www.selleckchem.com/products/apoptozole.html  As a result, CCNY was mainly expressed in lung cancer. CCNYc could promote cell motility and invasion. It indicated that CCNYc/PFTK1 complex could promote cell metastasis by regulating the formation of F-actin via TPM4.Fuchs' uveitis syndrome (FUS) is one of the most under- or misdiagnosed uveitis entities. Many undiagnosed FUS patients are unnecessarily overtreated with anti-inflammatory drugs, which may lead to serious complications. To offer assistance for ophthalmologists in the screening and diagnosis of FUS, we developed seven deep convolutional neural networks (DCNNs) to detect FUS using slit-lamp images. We also proposed a new optimized model with a mixed "attention" module to improve test accuracy. In the same independent set, we compared the performance between these DCNNs and ophthalmologists in detecting FUS. Seven different network models, including Xception, Resnet50, SE-Resnet50, ResNext50, SE-ResNext50, ST-ResNext50, and SET-ResNext50, were used to predict FUS automatically with the area under the receiver operating characteristic curves (AUCs) that ranged from 0.951 to 0.977. Our proposed SET-ResNext50 model (accuracy = 0.930; Precision = 0.918; Recall = 0.923; F1 measure = 0.920) with an AUC of 0.977 consistently outperformed the other networks and outperformed general ophthalmologists by a large margin. Heat-map visualizations of the SET-ResNext50 were provided to identify the target areas in the slit-lamp images. In conclusion, we confirmed that a trained classification method based on DCNNs achieved high effectiveness in distinguishing FUS from other forms of anterior uveitis. The performance of the DCNNs was better than that of general ophthalmologists and could be of value in the diagnosis of FUS.To cause the devastating rice blast disease, the hemibiotrophic fungus Magnaporthe oryzae produces invasive hyphae (IH) that are enclosed in a plant-derived interfacial membrane, known as the extra-invasive hyphal membrane (EIHM), in living rice cells. Little is known about when the EIHM is disrupted and how the disruption contributes to blast disease. Here we show that the disruption of the EIHM correlates with the hyphal growth stage in first-invaded susceptible rice cells. Our approach utilized GFP that was secreted from IH as an EIHM integrity reporter. Secreted GFP (sec-GFP) accumulated in the EIHM compartment but appeared in the host cytoplasm when the integrity of the EIHM was compromised. Live-cell imaging coupled with sec-GFP and various fluorescent reporters revealed that the loss of EIHM integrity preceded shrinkage and eventual rupture of the rice vacuole. The vacuole rupture coincided with host cell death, which was limited to the invaded cell with presumed closure of plasmodesmata. We report that EIHM disruption and host cell death are landmarks that delineate three distinct infection phases (early biotrophic, late biotrophic, and transient necrotrophic phases) within the first-invaded cell before reestablishment of biotrophy in second-invaded cells. M. oryzae effectors exhibited infection phase-specific localizations, including entry of the apoplastic effector Bas4 into the host cytoplasm through the disrupted EIHM during the late biotrophic phase. Understanding how infection phase-specific cellular dynamics are regulated and linked to host susceptibility will offer potential targets that can be exploited to control blast disease.