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IKKα promotes intestinal tumorigenesis by limiting recruitment of M1-like polarized myeloid cells
(2014)
The recruitment of immune cells into solid tumors is an essential prerequisite of tumor development. Depending on the prevailing polarization profile of these infiltrating leucocytes, tumorigenesis is either promoted or blocked. Here, we identify IκB kinase α (IKKα) as a central regulator of a tumoricidal microenvironment during intestinal carcinogenesis. Mice deficient in IKKα kinase activity are largely protected from intestinal tumor development that is dependent on the enhanced recruitment of interferon γ (IFNγ)-expressing M1-like myeloid cells. In IKKα mutant mice, M1-like polarization is not controlled in a cell-autonomous manner but, rather, depends on the interplay of both IKKα mutant tumor epithelia and immune cells. Because therapies aiming at the tumor microenvironment rather than directly at the mutated cancer cell may circumvent resistance development, we suggest IKKα as a promising target for colorectal cancer (CRC) therapy.
Type IV pili are flexible filaments on the surface of bacteria, consisting of a helical assembly of pilin proteins. They are involved in bacterial motility (twitching), surface adhesion, biofilm formation and DNA uptake (natural transformation). Here, we use cryo-electron microscopy and mass spectrometry to show that the bacterium Thermus thermophilus produces two forms of type IV pilus ("wide" and "narrow"), differing in structure and protein composition. Wide pili are composed of the major pilin PilA4, while narrow pili are composed of a so-far uncharacterized pilin which we name PilA5. Functional experiments indicate that PilA4 is required for natural transformation, while PilA5 is important for twitching motility.
The present research investigates if and how a more digitally centered communication between supervisors and employees satisfies employees’ needs regarding the communication with their supervisors and influences employees’ attitudes toward the supervisor and the job. In a cross-sectional online study, 261 employees rated their supervisors’ actual and ideal use of different communication channels (i.e., telephone, face-to-face, email) regarding quality and quantity. Employees’ job satisfaction and their perceptions of their supervisors’ effectiveness and team identification were measured as dependent variables. Employees perceived face-to-face communication to be of higher quality than telephone and email communication, and they indicated a preference for more face-to-face communication with their supervisors than they actually had. Moreover, the perceived quality of communication, especially via face-to-face, was strongly and positively related to the dependent variables. These results provide insights into potential problems of increasing e-leadership in organizations. We conclude with recommendations to reduce these problems.