SUMMARY Studies on the role of TP53 mutation in breast cancer response to chemotherapy are conflicting. Here, we show that, contrary to dogma, MMTV-Wnt1 mammary tumors with mutant p53 exhibited a superior clinical response compared to tumors with wild-type p53. Doxorubicin-treated p53-mutant tumors failed to arrest proliferation leading to abnormal mitoses and cell death, while p53 wild-type tumors arrested, avoiding mitotic catastrophe. Senescent tumor cells persisted, secreting senescence-associated cytokines that exhibited autocrine/paracrine activity and mitogenic potential. Wild-type p53 still mediated arrest and inhibited drug response even in the context of a heterozygous p53 point mutation or absence of p21. Thus, we show wild-type p53 activity hinders chemotherapy response and demonstrate the need to reassess the paradigm for p53 in cancer therapy.

The purpose of this study was to evaluate a novel instrumented mouthguard as a research device for measuring head impact kinematics. To evaluate kinematic accuracy, laboratory impact testing was performed at sites on the helmet and facemask for determining how closely instrumented mouthguard data matched data from an anthropomorphic test device. Laboratory testing results showed that peak linear acceleration (r2 = 0.96), peak angular acceleration (r2 = 0.89), and peak angular velocity (r2 = 0.98) measurements were highly correlated between the instrumented mouthguard and anthropomorphic test device. Normalized root-mean-square errors for impact time traces were 9.9 ± 4.4% for linear acceleration, 9.7 ± 7.0% for angular acceleration, and 10.4 ± 9.9% for angular velocity. This study demonstrates the potential of an instrumented mouthguard as a research tool for measuring in vivo impacts, which could help uncover the link between head impact kinematics and brain injury in American football.

Viruses that cause lysis of Synechococcus spp. are present throughout the year in the western Gulf of Mexico. The effect of sunlight on loss rates of cyanophage infectivity was determined by incubating natural cyanophage communities and cyanophage isolates (strains S-PWM1 and S-PWM3) in UV-transparent bags at the surface, and at depth, on several occasions throughout the year. Decay rates of infectivity of natural cyanophage communities at the surface, at Port Aransas, Texas, USA, ranged from undetectable to 0.335 h-1, with the highest rates occurring during the summer. During the spring and winter, decay rates of cyanophage isolates and natural cyanophage communities were generally similar, but during summer, decay rates of isolates were as much as twofold higher than the natural communities. In situ incubations at two offshore stations during a bloom of Synechococcus spp. produced decay rates of 0.53 and 0.75 d-1, integrated over the mixed layer and averaged over 24 h. Based on a burst size of 81 viruses produced per lysed cell (measured for natural cyanobacterial communities in the Gulf of Mexico), cyanophages imposed mortality rates of 1 and 8%, respectively, on Synechococcus spp. In contrast, in nearshore incubations in the winter and spring, cyanophages were responsible for removing <1% of the Synechococcus cells on a daily basis. Only an estimated 2 to 3% of contacts led to viral infections (based on theoretical contact rates between host cells and cyanophages, and estimates of cyanophage mortality), regardless of the time of year or concentrations of viruses and hosts. These results indicate that natural cyanophage communities tolerate damage by solar radiation better in summer than in winter. Moreover, net decay rates of cyanophage infectivity in sunlight were similar, whether host cells were present or not, indicating that detectable cyanophage production did not occur during daytime in situ incubations.

Only 492 of 11 859 publications actually assessed the effectiveness of sports injury prevention interventions or their implementation. Research in the area of regulatory change is underrepresented and might represent one of the greatest opportunities to prevent injury.