Mitochondrial DNA (mtDNA) is highly polymorphic, and host mtDNA variation has been associated with altered cancer severity. To determine the basis of this mtDNA-cancer association, we analyzed conplastic mice with the C57BL/6J (B6) nucleus but two naturally occurring mtDNA lineages, and , where mitochondria generate more oxidative phosphorylation (OXPHOS)-derived reactive oxygen species (mROS). In a cardiac transplant model, Foxp3+ T regulatory (Treg) cells supported long-term allograft survival, whereas Treg cells failed to suppress host T effector (Teff) cells, leading to acute rejection.
View Article and Find Full Text PDFBidirectional cargo transport by kinesin and dynein is essential for cell viability and defects are linked to neurodegenerative diseases. The competition between motors is described as a tug-of-war, and computational modeling suggests that the load-dependent off-rate is the strongest determinant of which motor 'wins'. Optical tweezer experiments find that the load-dependent detachment sensitivity of transport kinesins is kinesin-3 > kinesin-2 > kinesin-1.
View Article and Find Full Text PDFOn April 24, 2023, the American Samoa Department of Health (ASDoH) declared a public health emergency amid concern about a possible measles outbreak given low 2-dose vaccination coverage at the time. ASDoH had received two positive measles immunoglobulin (Ig) M test results after Flag Day festivities 1 week earlier from vaccinated children. ASDoH performed active case finding, took actions to mitigate transmission, and requested technical assistance from CDC.
View Article and Find Full Text PDFIntracellular vesicles are typically transported by a small number of kinesin and dynein motors. However, the slow microtubule binding rate of kinesin-1 observed in biophysical studies suggests that long-range transport may require a high number of motors. To address the discrepancy in motor requirements between and studies, we reconstituted motility of 120-nm-diameter liposomes driven by multiple GFP-labeled kinesin-1 motors.
View Article and Find Full Text PDFCytoplasmic dynein-1 (dynein), the primary retrograde motor in most eukaryotes, supports the movement of hundreds of distinct cargos, each with specific trafficking requirements. To achieve this functional diversity, dynein must bind to the multi-subunit complex dynactin and one of a family of cargo adaptors to be converted into an active, processive motor complex. Very little is known about the dynamic processes that promote the formation of this complex.
View Article and Find Full Text PDF