Background: Progesterone Receptor Membrane Component 1 (PGRMC1) is expressed in many cancer cells, where it is associated with detrimental patient outcomes. It contains phosphorylated tyrosines which evolutionarily preceded deuterostome gastrulation and tissue differentiation mechanisms. Results: We demonstrate that manipulating PGRMC1 phosphorylation status in MIA PaCa-2 (MP) cells imposes broad pleiotropic effects. Relative to parental cells over-expressing hemagglutinin-tagged wild-type (WT) PGRMC1-HA, cells expressing a PGRMC1-HA-S57A/S181A double mutant (DM) exhibited reduced levels of proteins involved in energy metabolism and mitochondrial function, and altered glucose metabolism suggesting modulation of the Warburg effect. This was associated with increased PI3K/Akt activity, altered cell shape, actin cytoskeleton, motility, and mitochondrial properties. An S57A/Y180F/S181A triple mutant (TM) indicated the involvement of Y180 in PI3K/Akt activation. Mutation of Y180F strongly attenuated subcutaneous xenograft tumor growth in NOD-SCID gamma mice. Elsewhere we demonstrate altered metabolism, mutation incidence, and epigenetic status in these cells. Conclusions: Altogether, these results indicate that mutational manipulation of PGRMC1 phosphorylation status exerts broad pleiotropic effects relevant to cancer and other cell biology.
Cervical cancer has become the third most common form of cancer in the in-universe, after the widespread breast cancer. Human papillomavirus risk of infection is linked to the majority of cancer cases. Preventive care, the most expensive way of fighting cancer, can protect about 37% of cancer cases. The Pap smear examination is a standard screening procedure for the initial screening of cervical cancer. However, this manual test procedure generates many false-positive outcomes due to individual errors. Various researchers have extensively investigated machine learning (ML) methods for classifying cervical Pap cells to enhance manual testing. The random forest method is the most popular method for anticipating features from a high-dimensional cancer image dataset. However, the random forest method can get too slow and inefficient for real-time forecasts when too many decision trees are used. This research proposed an efficient feature selection and prediction model for cervical cancer datasets using Boruta analysis and SVM method to deal with this challenge. A Boruta analysis method is used. It is improved from of random forest method and mainly discovers feature subsets from the data source that are significant to assigned classification activity. The proposed model’s primary aim is to determine the importance of cervical cancer screening factors for classifying high-risk patients depending on the findings. This research work analyses cervical cancer and various risk factors to help detect cervical cancer. The proposed model Boruta with SVM and various popular ML models are implemented using Python and various performance measuring parameters, i.e., accuracy, precision, F 1 – Score , and recall. However, the proposed Boruta analysis with SVM performs outstanding over existing methods.
Background: Progesterone Receptor Membrane Component 1 (PGRMC1) is expressed in many cancer cells, where it is associated with detrimental patient outcomes. It contains phosphorylated tyrosines which evolutionarily preceded deuterostome gastrulation and tissue differentiation mechanisms. Results: We demonstrate that manipulating PGRMC1 phosphorylation status in MIA PaCa-2 (MP) cells imposes broad pleiotropic effects. Relative to parental cells over-expressing hemagglutinin-tagged wild-type (WT) PGRMC1-HA, cells expressing a PGRMC1-HA-S57A/S181A double mutant (DM) exhibited reduced levels of proteins involved in energy metabolism and mitochondrial function, and altered glucose metabolism suggesting modulation of the Warburg effect. This was associated with increased PI3K/Akt activity, altered cell shape, actin cytoskeleton, motility, and mitochondrial properties. An S57A/Y180F/S181A triple mutant (TM) indicated the involvement of Y180 in PI3K/Akt activation. Mutation of Y180F strongly attenuated subcutaneous xenograft tumor growth in NOD-SCID gamma mice. Elsewhere we demonstrate altered metabolism, mutation incidence, and epigenetic status in these cells. Conclusions: Altogether, these results indicate that mutational manipulation of PGRMC1 phosphorylation status exerts broad pleiotropic effects relevant to cancer and other cell biology.
Citrus fruit diseases have an egregious impact on both the quality and quantity of the citrus fruit production and market. Automatic detection of severity is essential for the high-quality production of fruit. In the current work, a citrus fruit dataset is preprocessed by rescaling and establishing bounding boxes with labeled image software. Then, a selective search, which combines the capabilities of both an extensive search and graph-based segmentation, is applied. The proposed deep neural network (DNN) model is trained to detect targeted areas of the disease with its severity level using citrus fruits that have been labeled with the help of a domain expert with four severity levels (high, medium, low and healthy) as ground truth. Transfer learning using VGGNet is applied to implement a multi-classification framework for each class of severity. The model predicts the low severity level with 99% accuracy, and the high severity level with 98% accuracy. The model demonstrates 96% accuracy in detecting healthy conditions and 97% accuracy in detecting medium severity levels. The result of the work shows that the proposed approach is valid, and it is efficient for detecting citrus fruit disease at four levels of severity.
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