Cytidine deaminase-dependent mitochondrial biogenesis as a potential vulnerability in pancreatic cancer cells.

Cytidine deaminase (CDA) converts cytidine and deoxycytidine into uridine and deoxyuridine as part of the pyrimidine salvage pathway. Elevated levels of CDA are found in pancreatic tumors and associated with chemoresistance. Recent evidence suggests that CDA has additional functions in cancer cell biology.

Psychiatric Diagnosis: A Clinical Guide to Navigating Diagnostic Pluralism.

The controversies surrounding the Diagnostic and Statistical Manual of Mental Disorders and International Classification of Diseases have generated significant debate across the psy-sciences. This debate has been further fueled by the launch of the Research Domain Criteria as a framework to facilitate advances in neuroscientific research, a renewed emphasis on dimensional models of psychopathology, currently exemplified by the Hierarchical Taxonomy of Psychopathology, and development of the Psychodynamic Diagnostic Manual by the psychodynamic community. In this article, we provide a clinical overview of recent debates surrounding categorical and dimensional approaches to psychiatric diagnosis, offer a critical assessment of proposed alternatives, and discuss how clinicians can navigate a plurality of diagnostic frameworks.

Cytidine Deaminase Resolves Replicative Stress and Protects Pancreatic Cancer from DNA-Targeting Drugs.

Unlabelled: Cytidine deaminase (CDA) functions in the pyrimidine salvage pathway for DNA and RNA syntheses and has been shown to protect cancer cells from deoxycytidine-based chemotherapies. In this study, we observed that CDA was overexpressed in pancreatic adenocarcinoma from patients at baseline and was essential for experimental tumor growth. Mechanistic investigations revealed that CDA localized to replication forks where it increased replication speed, improved replication fork restart efficiency, reduced endogenous replication stress, minimized DNA breaks, and regulated genetic stability during DNA replication.