Ablation of the dystrophin Dp71f alternative C-terminal variant increases sarcoma tumour cell aggressiveness.

Alterations in Dp71 expression, the most ubiquitous dystrophin isoform, have been associated with patient survival across tumours. Intriguingly, in certain malignancies, Dp71 acts as a tumour suppressor, while manifesting oncogenic properties in others. This diversity could be explained by the expression of two Dp71 splice variants encoding proteins with distinct C-termini, each with specific properties. Expression of these variants has impeded the exploration of their unique roles. Using CRISPR/Cas9, we ablated the Dp71f variant with the alternative C-terminus in a sarcoma cell line not expressing the canonical C-terminal variant, and conducted molecular (RNAseq) and functional characterisation of the knockout cells. Dp71f ablation induced major transcriptomic alterations, particularly affecting the expression of genes involved in calcium signalling and ECM-receptor interaction pathways. The genome-scale metabolic analysis identified significant downregulation of glucose transport via membrane vesicle reaction (GLCter) and downregulated glycolysis/gluconeogenesis pathway. Functionally, these molecular changes corresponded with, increased calcium responses, cell adhesion, proliferation, survival under serum starvation and chemotherapeutic resistance. Knockout cells showed reduced GLUT1 protein expression, survival without attachment and their migration and invasion in vitro and in vivo were unaltered, despite increased matrix metalloproteinases release. Our findings emphasise the importance of alternative splicing of dystrophin transcripts and underscore the role of the Dp71f variant, which appears to govern distinct cellular processes frequently dysregulated in tumour cells. The loss of this regulatory mechanism promotes sarcoma cell survival and treatment resistance. Thus, Dp71f is a target for future investigations exploring the intricate functions of specific DMD transcripts in physiology and across malignancies.

DRL-GAN: A Hybrid Approach for Binary and Multiclass Network Intrusion Detection.

Our increasingly connected world continues to face an ever-growing number of network-based attacks. An Intrusion Detection System (IDS) is an essential security technology used for detecting these attacks. Although numerous Machine Learning-based IDSs have been proposed for the detection of malicious network traffic, the majority have difficulty properly detecting and classifying the more uncommon attack types. In this paper, we implement a novel hybrid technique using synthetic data produced by a Generative Adversarial Network (GAN) to use as input for training a Deep Reinforcement Learning (DRL) model. Our GAN model is trained on the NSL-KDD dataset, a publicly available collection of labeled network traffic data specifically designed to support the evaluation and benchmarking of IDSs. Ultimately, our findings demonstrate that training the DRL model on synthetic datasets generated by specific GAN models can result in better performance in correctly classifying minority classes over training on the true imbalanced dataset.

COVID-19 Pandemic and the Convalescent Plasma Therapy: Possible Benefits and Risks.

PURPOSE OF REVIEW: COVID-19 pandemic has been the major threat to the global public health for a year (last of 2019-till date); and unfortunately, there is still as no specific antiviral agent which can be effectively used against this disease curation. Present review focused on the application of the convalescent plasma (CP) therapy as a quick remediation of the disease severity. RECENT FINDINGS: While several drugs have been repurposed based on a number of completed clinical trials together with a huge ongoing effort to develop appropriate vaccine against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the therapeutic approach of the CP therapy appears to be one of the effective methods to rescue the severely affected COVID-19 patients. Such a therapy based on passive immunity evolved from the SARS-CoV-2-infected patients who have fully recovered from COVID-19; and hence these individuals are quite likely to possess high titers of the SARS-CoV-2-neutralizing immunoglobulins (antibodies). However, there are some risks such therapy, and its effectivity also appeared doubtful in some cases. Thus, the current review discussed the issues raised by the administration of such plasma into the SARS-CoV-2-infected individuals. SUMMARY: Application of CP therapy has been conducted since long time; and for the mitigation of COVID-19 severity, such pharmaceutical strategy is also being employed in spite of several risks which actually can be monitored as well as optimized in order to combat the SARS-CoV-2 infection.