Genomic aberrations after short-term exposure to colibactin-producing E. coli transform primary colon epithelial cells

Genotoxic colibactin-producing pks+ Escherichia coli induce DNA double-strand breaks, mutations, and promote tumor development in mouse models of colorectal cancer (CRC). Colibactin’s distinct mutational signature is reflected in human CRC, suggesting a causal link. Here, we investigate its transformation potential using organoids from primary murine colon epithelial cells. Organoids recovered from short-term infection with pks+ E. coli show characteristics of CRC cells, e.g., enhanced proliferation, Wnt-independence, and impaired differentiation. Sequence analysis of Wnt-independent organoids reveals an enhanced mutational burden, including chromosomal aberrations typical of genomic instability. Although we do not find classic Wnt-signaling mutations, we identify several mutations in genes related to p53-signaling, including miR-34a. Knockout of Trp53 or miR-34 in organoids results in Wnt-independence, corroborating a functional interplay between the p53 and Wnt pathways. We propose larger chromosomal alterations and aneuploidy as the basis of transformation in these organoids, consistent with the early appearance of chromosomal instability in CRC

Using Cognitive Ubiquitous Robots for Assisting Dependent People in Smart Spaces

International audienceIn this chapter we discuss the necessity to move beyond built-in monotonic semantic web based reasoning-architectures for endowing ubiquitous robots with cognitive capabilities, which are strongly required in ambient assistive living, towards new architectures that combine different reasoning mechanisms to achieve better context awareness and adaptability in dynamic environments. We also present practical reasoning approaches that we have developed during the last decade for ambient intelligence and robotics applications. Finally, we discuss future directions that should be investigated to implement high-level cognitive capabilities that can be supported by cloud computing platforms as reasoning backend for robots and connected devices in smart spaces. These will enhance the human-environment interaction using robots, emergency prevention, management and rescue

Using Cognitive Ubiquitous Robots for Assisting Dependent People in Smart Spaces

International audienceIn this chapter we discuss the necessity to move beyond built-in monotonic semantic web based reasoning-architectures for endowing ubiquitous robots with cognitive capabilities, which are strongly required in ambient assistive living, towards new architectures that combine different reasoning mechanisms to achieve better context awareness and adaptability in dynamic environments. We also present practical reasoning approaches that we have developed during the last decade for ambient intelligence and robotics applications. Finally, we discuss future directions that should be investigated to implement high-level cognitive capabilities that can be supported by cloud computing platforms as reasoning backend for robots and connected devices in smart spaces. These will enhance the human-environment interaction using robots, emergency prevention, management and rescue

Using Cognitive Ubiquitous Robots for Assisting Dependent People in Smart Spaces

International audienceIn this chapter we discuss the necessity to move beyond built-in monotonic semantic web based reasoning-architectures for endowing ubiquitous robots with cognitive capabilities, which are strongly required in ambient assistive living, towards new architectures that combine different reasoning mechanisms to achieve better context awareness and adaptability in dynamic environments. We also present practical reasoning approaches that we have developed during the last decade for ambient intelligence and robotics applications. Finally, we discuss future directions that should be investigated to implement high-level cognitive capabilities that can be supported by cloud computing platforms as reasoning backend for robots and connected devices in smart spaces. These will enhance the human-environment interaction using robots, emergency prevention, management and rescue

Genomic aberrations after short-term exposure to colibactin-producing E. coli transform primary colon epithelial cells

Genotoxic colibactin-producing pks+ Escherichia coli induce DNA double-strand breaks, mutations, and promote tumor development in mouse models of colorectal cancer (CRC). Colibactin’s distinct mutational signature is reflected in human CRC, suggesting a causal link. Here, we investigate its transformation potential using organoids from primary murine colon epithelial cells. Organoids recovered from short-term infection with pks+ E. coli show characteristics of CRC cells, e.g., enhanced proliferation, Wnt-independence, and impaired differentiation. Sequence analysis of Wnt-independent organoids reveals an enhanced mutational burden, including chromosomal aberrations typical of genomic instability. Although we do not find classic Wnt-signaling mutations, we identify several mutations in genes related to p53-signaling, including miR-34a. Knockout of Trp53 or miR-34 in organoids results in Wnt-independence, corroborating a functional interplay between the p53 and Wnt pathways. We propose larger chromosomal alterations and aneuploidy as the basis of transformation in these organoids, consistent with the early appearance of chromosomal instability in CRC