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SUMOylation-mediated PSME3-20S Proteasomal Degradation of Transcription Factor CP2c is Crucial for Cell Cycle Progression
No full textTranscription factor CP2c (also known as TFCP2, α-CP2, LSF, and LBP-1c) is involved in diverse ubiquitous and tissue/stage-specific cellular processes and in human malignancies such as cancer. Despite its importance, many fundamental regulatory mechanisms of CP2c are still unclear. Here, we uncover an unprecedented mechanism of CP2c degradation via a previously unidentified SUMO1/PSME3/20S proteasome pathway and its biological meaning. CP2c is SUMOylated in a SUMO1-dependent way, and SUMOylated CP2c is degraded through the ubiquitin-independent PSME3 (also known as REGγ or PA28)/20S proteasome system. SUMOylated PSME3 could also interact with CP2c to degrade CP2c via the 20S proteasomal pathway. Moreover, precisely timed degradation of CP2c via the SUMO1/PSME3/20S proteasome axis is required for accurate progression of the cell cycle. Therefore, we reveal a unique SUMO1-mediated uncanonical 20S proteasome degradation mechanism via the SUMO1/PSME3 axis involving mutual SUMO-SIM interaction of CP2c and PSME3, providing previously unidentified mechanistic insights into the roles of dynamic degradation of CP2c in cell cycle progression
Biomolecular Condensates: Insights Into Early and Late Steps of the HIV-1 Replication Cycle
No full textA rapidly evolving understanding of phase separation in the biological and physical sciences has led to the redefining of virus-engineered replication compartments in many viruses with RNA genomes. Condensation of viral, host and genomic and subgenomic RNAs can take place to evade the innate immunity response and to help viral replication. Divergent viruses prompt liquid–liquid phase separation (LLPS) to invade the host cell. During HIV replication there are several steps involving LLPS. In this review, we characterize the ability of individual viral and host partners that assemble into biomolecular condensates (BMCs). Of note, bioinformatic analyses predict models of phase separation in line with several published observations. Importantly, viral BMCs contribute to function in key steps retroviral replication. For example, reverse transcription takes place within nuclear BMCs, called HIV-MLOs while during late replication steps, retroviral nucleocapsid acts as a driver or scaffold to recruit client viral components to aid the assembly of progeny virions. Overall, LLPS during viral infections represents a newly described biological event now appreciated in the virology field, that can also be considered as an alternative pharmacological target to current drug therapies especially when viruses become resistant to antiviral treatment
Stakeholder-based problems in the local benefit chain of tourism: A study in Adıyaman
No full textThe geographical movement of large human societies is the phenomenal phenomenon of our time. This mobility is also a social event, and the cause-effect relationship has an impact area extending from the individual to the general. Similarly, tourism as a system is complex. Each element constituting this system operates on the axis of different purposes and processes and affects the tourism system. Based on this starting point, this study aims to examine tourism development problems in Adıyaman. In the research, data were collected from eight (8) tourism stakeholders between 05.01.2022 and 15.02.2022 by semi-structured interview method. The data were analyzed by content analysis and descriptive analysis methods. The results of the research show that the primary problem in tourism development in Adıyaman is the lack of publicity. However, it was determined that bureaucratic support, service quality, lack of cooperation and coordination are other factors that limit tourism development. On the axis of the research results, theoretical and managerial suggestions were made
COVID Learning Loss: A Call to Action
No full textThe COVID-19 pandemic and policy responses designed to mitigate transmission have caused deep and persistent mathematics learning loss among K–12 students. While initial data might have been read optimistically as a blip that would reverse once schools returned to normal, 2023 data from the National Assessment of Educational Progress (NAEP) show that losses persist. While the NAEP does not directly measure quantitative reasoning (QR), the data present a disturbing picture for QR instruction and call for new lines of research that inform QR pedagogical response
Damage identification in 3D printed metal parts using deep learning
No full textAn active Structural Health Monitoring (SHM) method called Surface Response to Excitation (SuRE), is used in this study to detect and quantify the damages created by a milling operation on additively manufactured metal plates. This method entails bonding two piezoelectric disks to the test specimens, one to excite it with surface waves from one end of the plate, and the other to sense the dynamic response to excitation at the other end. A sweep sine wave with a duration of 1 ms, ranging from 50-120 kHz is used as the excitation signal. Five stainless steel plates of identical size (195×54×2.5 mm) were created using a Markforged metal 3D printer. The data for four different conditions were recorded, which are, when the parts were undamaged and when they were face milled at 3 different lengths. The data was then used to train One-Dimensional and Two-Dimensional Convolutional Neural Networks (CNN) and also a Long Short-Term Memory (LSTM) neural network. The continuous wavelet transform (CWT) was used to convert the collected sensor data from the time domain to time-frequency representation images to be classified by the 2D CNN. The 1D CNN, 2D CNN and the LSTM classified the damage length with an overall accuracy of 98.9%, 100%, and 97.8% respectfully