MSH2/MSH6 Complex Promotes Error-Free Repair of AID-Induced dU:G Mispairs as well as Error-Prone Hypermutation of A:T Sites

Mismatch repair of AID-generated dU:G mispairs is critical for class switch recombination (CSR) and somatic hypermutation (SHM) in B cells. The generation of a previously unavailable Msh2−/−Msh6−/− mouse has for the first time allowed us to examine the impact of the complete loss of MutSα on lymphomagenesis, CSR and SHM. The onset of T cell lymphomas and the survival of Msh2−/−Msh6−/− and Msh2−/−Msh6−/−Msh3−/− mice are indistinguishable from Msh2−/− mice, suggesting that MSH2 plays the critical role in protecting T cells from malignant transformation, presumably because it is essential for the formation of stable MutSα heterodimers that maintain genomic stability. The similar defects on switching in Msh2−/−, Msh2−/−Msh6−/− and Msh2−/−Msh6−/−Msh3−/− mice confirm that MutSα but not MutSβ plays an important role in CSR. Analysis of SHM in Msh2−/−Msh6−/− mice not only confirmed the error-prone role of MutSα in the generation of strand biased mutations at A:T bases, but also revealed an error-free role of MutSα when repairing some of the dU:G mispairs generated by AID on both DNA strands. We propose a model for the role of MutSα at the immunoglobulin locus where the local balance of error-free and error-prone repair has an impact in the spectrum of mutations introduced during Phase 2 of SHM

Cognitive intelligence: deep learning, thinking, and reasoning by brain-inspired systems

The theme of IEEE ICCI*CC'16 on Cognitive Informatics (CI) and Cognitive Computing (CC) was on cognitive computers, big data cognition, and machine learning. CI and CC are a contemporary field not only for basic studies on the brain, computational intelligence theories, and denotational mathematics, but also for engineering applications in cognitive systems towards deep learning, deep thinking, and deep reasoning. This paper reports a set of position statements presented in the plenary panel (Part I) in IEEE ICCI*CC'16 at Stanford University. The summary is contributed by invited panelists who are part of the world's renowned scholars in the transdisciplinary field of CI and CC

Cognitive intelligence: deep learning, thinking, and reasoning by brain-inspired systems

The theme of IEEE ICCI*CC'16 on Cognitive Informatics (CI) and Cognitive Computing (CC) was on cognitive computers, big data cognition, and machine learning. CI and CC are a contemporary field not only for basic studies on the brain, computational intelligence theories, and denotational mathematics, but also for engineering applications in cognitive systems towards deep learning, deep thinking, and deep reasoning. This paper reports a set of position statements presented in the plenary panel (Part I) in IEEE ICCI*CC'16 at Stanford University. The summary is contributed by invited panelists who are part of the world's renowned scholars in the transdisciplinary field of CI and CC

Cognitive intelligence: deep learning, thinking, and reasoning by brain-inspired systems

The theme of IEEE ICCI*CC'16 on Cognitive Informatics (CI) and Cognitive Computing (CC) was on cognitive computers, big data cognition, and machine learning. CI and CC are a contemporary field not only for basic studies on the brain, computational intelligence theories, and denotational mathematics, but also for engineering applications in cognitive systems towards deep learning, deep thinking, and deep reasoning. This paper reports a set of position statements presented in the plenary panel (Part I) in IEEE ICCI*CC'16 at Stanford University. The summary is contributed by invited panelists who are part of the world's renowned scholars in the transdisciplinary field of CI and CC