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.

Microorganisms and the viruses that infect them are the most numerous biological entities on Earth and enclose its greatest biodiversity and genetic reservoir. With strength in their numbers, these microscopic organisms are major players in the cycles of energy and matter that sustain all life. Scientists have only scratched the surface of this vast microbial world through culture-dependent methods. Recent developments in generating metagenomes, large random samples of nucleic acid sequences isolated directly from the environment, are providing comprehensive portraits of the composition, structure, and functioning of microbial communities. Moreover, advances in metagenomic analysis have created the possibility of obtaining complete or nearly complete genome sequences from uncultured microorganisms, providing important means to study their biology, ecology, and evolution. Here we review some of the recent developments in the field of metagenomics, focusing on the discovery of genetic novelty and on methods for obtaining uncultured genome sequences, including through the recycling of previously published datasets. Moreover we discuss how metagenomics has become a core scientific tool to characterize eco-evolutionary patterns of microbial ecosystems, thus allowing us to simultaneously discover new microbes and study their natural communities. We conclude by discussing general guidelines and challenges for modeling the interactions between uncultured microorganisms and viruses based on the information contained in their genome sequences. These models will significantly advance our understanding of the functioning of microbial ecosystems and the roles of microbes in the environment.

The environmental metabolome and metabolic potential of microorganisms are dominant and essential factors shaping microbial community composition. Recent advances in genome annotation and systems biology now allow us to semiautomatically reconstruct genome-scale metabolic models (GSMMs) of microorganisms based on their genome sequence . Next, growth of these models in a defined metabolic environment can be predicted in silico, mechanistically linking the metabolic fluxes of individual microbial populations to the community dynamics. A major advantage of GSMMs is that no training data is needed, besides information about the metabolic capacity of individual genes (genome annotation) and knowledge of the available environmental metabolites that allow the microorganism to grow. However, the composition of the environment is often not fully determined and remains difficult to measure . We hypothesized that the relative abundance of different bacterial species, as measured by metagenomics, can be combined with GSMMs of individual bacteria to reveal the metabolic status of a given biome. Using a newly developed algorithm involving over 1,500 GSMMs of human-associated bacteria, we inferred distinct metabolomes for four human body sites that are consistent with experimental data. Together, we link the metagenome to the metabolome in a mechanistic framework towards predictive microbiome modelling.

Mass ECG screening is achievable within the collegiate setting by using volunteers when the appropriate equipment is available. However, the rate of secondary testing suggests the need for an evaluation of cost-effectiveness for mass screening and the development of new athlete-specific ECG interpretation algorithms.

We investigated the potential for photoreactivation to restore infectivity to sunlight-damaged natural viral communities in offshore (chlorophyll a, <0.1 g liter ؊1), coastal (chlorophyll a, ca. 0.2 g liter ؊1), and estuarine (chlorophyll a, ca. 1 to 5 g liter ؊1) waters of the Gulf of Mexico. In 67% of samples, the lightdependent repair mechanisms of the bacterium Vibrio natriegens restored infectivity to natural viral communities which could not be repaired by light-independent mechanisms. Similarly, exposure of sunlight-damaged natural viral communities to >312-nm-wavelength sunlight in the presence of the natural bacterial communities restored infectivity to 21 to 26% of sunlight-damaged viruses in oceanic waters and 41 to 52% of the damaged viruses in coastal and estuarine waters. Wavelengths between 370 and 550 nm were responsible for restoring infectivity to the damaged viruses. These results indicate that light-dependent repair, probably photoreactivation, compensated for a large fraction of sunlight-induced DNA damage in natural viral communities and is potentially essential for the maintenance of high concentrations of viruses in surface waters.