Expression of Interleukin-8 Promotes Neutrophil Infiltration and Genetic Instability in Mutatect Tumors

Neutrophils represent a potential source of genotoxic reactive oxygen and nitrogen species in the tumor microenvironment. Using Mutatect cell lines, which can form subcutaneous tumors in syngeneic C57BL/6 mice, we have previously established that the number of spontaneously infiltrating neutrophils correlates with the number of mutations at the hypoxanthine phosphoribosyltransferase (Hprt) locus. We now describe the properties of four lines that express different levels of the neutrophil chemokine, interleukin-8 (IL-8), from a tetracycline (TET)-responsive promoter. In a series involving 45 animals, IL-8-expressing lines produced tumors with a higher neutrophil content than the control line. Analysis of the 45 tumors revealed that the neutrophil level again strongly correlated with hprt mutant frequency (MF) (P<.0001, r=0.88). Administration of TET was effective in lowering the neutrophil content of low IL-8-expressing tumors, but not high IL-8-expressing tumors. Although the IL-8 transgene was stable in all lines in vitro, high IL-8-expressing lines completely lost the transgene in vivo whereas low IL-8-expressing lines showed no evidence of transgene instability. These results provide further evidence, based on the study of an endogenous gene (hprt) and an IL-8 transgene, that neutrophils may contribute to genetic instability in tumors

Predictors of self-reported symptoms and testing for COVID-19 in Canada using a nationally representative survey.

Random population-based surveys to estimate prevalence of SARS-CoV2 infection causing coronavirus disease (COVID-19) are useful to understand distributions and predictors of the infection. In April 2020, the first-ever nationally representative survey in Canada polled 4,240 adults age 18 years and older about self-reported COVID experience in March, early in the epidemic. We examined the levels and predictors of COVID symptoms, defined as fever plus difficulty breathing/shortness of breath, dry cough so severe that it disrupts sleep, and/or loss of sense of smell; and testing for SARS-CoV-2 by respondents and/or household members. About 8% of Canadians reported that they and/or one or more household members experienced COVID symptoms. Symptoms were more common in younger than in older adults, and among visible minorities. Overall, only 3% of respondents and/or household members reported testing for SARS-CoV-2. Being tested was associated with having COVID symptoms, Indigenous identity, and living in Quebec. Periodic nationally representative surveys of symptoms, as well as SARS-CoV-2 antibodies, are required in many countries to understand the pandemic and prepare for the future

Effective Thermal and Electrical Conductivities of AgSnO2 During Sintering. Part I Experimental Characterization and Mechanisms

The effective thermal and electrical conductivities of porous materials have a major influence on the temperature field inside the sample during resistance sintering (RS). Thermal and electrical effective conductivities of AgSnO2 can be calculated during sintering by using numerical modeling with constitutive equations, which consider microstructural transformations. In Part I of this investigation, the emphasis is on the development of an understanding of the microstructure-conductivity relationship starting from the "green" state to the fully sintered state during RS of AgSnO2. This work focuses on the characterization of the electrical and thermal effective conductivities of the porous composite material (AgSnO2), and on highlighting the mechanisms, which drive the evolutions of the effective conductivities and the microstructure. Measurements were achieved under different loadings (cold compaction, free sintering, Hot Pressing (HP), and RS). Results show that conductivities evolutions are mainly driven by the contact conditions between particles. Bonding diffusion between particles and grain deformation was identified as the main mechanism, which can enhance the contact area between particles. This work will provide all the essential information to define the constitutive equations, presented in details in Part II, to describe the evolutions of the effective conductivities during sintering processes, such as RS or HP