A New Mouse Model for the Study of Human Breast Cancer Metastasis

Breast cancer is the most common cancer in women, and this prevalence has a major impact on health worldwide. Localized breast cancer has an excellent prognosis, with a 5-year relative survival rate of 85%. However, the survival rate drops to only 23% for women with distant metastases. To date, the study of breast cancer metastasis has been hampered by a lack of reliable metastatic models. Here we describe a novel in vivo model using human breast cancer xenografts in NOD scid gamma (NSG) mice; in this model human breast cancer cells reliably metastasize to distant organs from primary tumors grown within the mammary fat pad. This model enables the study of the entire metastatic process from the proper anatomical site, providing an important new approach to examine the mechanisms underlying breast cancer metastasis. We used this model to identify gene expression changes that occur at metastatic sites relative to the primary mammary fat pad tumor. By comparing multiple metastatic sites and independent cell lines, we have identified several gene expression changes that may be important for tumor growth at distant sites

Assessing adolescents' critical health literacy: How is trust in government leadership associated with knowledge of COVID-19?

This study explored relations between COVID-19 news source, trust in COVID-19 information source, and COVID-19 health literacy in 194 STEM-oriented adolescents and young adults from the US and the UK. Analyses suggest that adolescents use both traditional news (e.g., TV or newspapers) and social media news to acquire information about COVID-19 and have average levels of COVID-19 health literacy. Hierarchical linear regression analyses suggest that the association between traditional news media and COVID-19 health literacy depends on participants' level of trust in their government leader. For youth in both the US and the UK who used traditional media for information about COVID-19 and who have higher trust in their respective government leader (i.e., former US President Donald Trump and UK Prime Minister Boris Johnson) had lower COVID-19 health literacy. Results highlight how youth are learning about the pandemic and the importance of not only considering their information source, but also their levels of trust in their government leaders

Interest and learning in informal science learning sites: Differences in experiences with different types of educators.

This study explored topic interest, perceived learning and actual recall of exhibit content in 979 children and adolescents and 1,184 adults who visited informal science learning sites and interacted with an adult or youth educator or just the exhibit itself as part of family visits to the sites. Children in early childhood reported greater topic interest and perceived learning, but actually recalled less content, than participants in middle childhood or adolescence. Youth visitors reported greater interest after interacting with a youth educator than just the exhibit, and perceived that they learn more if they interact with an educator (youth or adult). Participants in middle childhood recall more when they encounter a youth educator. Adult visitors reported greater interest after interaction with a youth educator than with the exhibit alone or an adult educator. They also perceived that they learn more if they interact with an educator (youth or adult) than just the exhibit and perceived that they learned more if they interacted with a youth educator than an adult educator. Results highlight the benefits of educators in informal science learning sites and document the importance of attention to developmental needs

Science and Math Interest and Gender Stereotypes: The Role of Educator Gender in Informal Science Learning Sites

Interest in science and math plays an important role in encouraging STEM motivation and career aspirations. This interest decreases for girls between late childhood and adolescence. Relatedly, positive mentoring experiences with female teachers can protect girls against losing interest. The present study examines whether visitors to informal science learning sites (ISLS; science centers, zoos, and aquariums) differ in their expressed science and math interest, as well as their science and math stereotypes following an interaction with either a male or female educator. Participants (n = 364; early childhood, n = 151, Mage = 6.73; late childhood, n = 136, Mage = 10.01; adolescence, n = 59, Mage = 13.92) were visitors to one of four ISLS in the United States and United Kingdom. Following an interaction with a male or female educator, they reported their math and science interest and responded to math and science gender stereotype measures. Female participants reported greater interest in math following an interaction with a female educator, compared to when they interacted with a male educator. In turn, female participants who interacted with a female educator were less likely to report male-biased math gender stereotypes. Self-reported science interest did not differ as a function of educator gender. Together these findings suggest that, when aiming to encourage STEM interest and challenge gender stereotypes in informal settings, we must consider the importance of the gender of educators and learners

Science and Math Interest and Gender Stereotypes: The Role of Educator Gender in Informal Science Learning Sites

Interest in science and math plays an important role in encouraging STEM motivation and career aspirations. This interest decreases for girls between late childhood and adolescence. Relatedly, positive mentoring experiences with female teachers can protect girls against losing interest. The present study examines whether visitors to informal science learning sites (ISLS; science centers, zoos, and aquariums) differ in their expressed science and math interest, as well as their science and math stereotypes following an interaction with either a male or female educator. Participants (n = 364; early childhood, n = 151, Mage = 6.73; late childhood, n = 136, Mage = 10.01; adolescence, n = 59, Mage = 13.92) were visitors to one of four ISLS in the United States and United Kingdom. Following an interaction with a male or female educator, they reported their math and science interest and responded to math and science gender stereotype measures. Female participants reported greater interest in math following an interaction with a female educator, compared to when they interacted with a male educator. In turn, female participants who interacted with a female educator were less likely to report male-biased math gender stereotypes. Self-reported science interest did not differ as a function of educator gender. Together these findings suggest that, when aiming to encourage STEM interest and challenge gender stereotypes in informal settings, we must consider the importance of the gender of educators and learners

High-Resolution Analysis of Parent-of-Origin Allelic Expression in the Arabidopsis Endosperm

Genomic imprinting is an epigenetic phenomenon leading to parent-of-origin specific differential expression of maternally and paternally inherited alleles. In plants, genomic imprinting has mainly been observed in the endosperm, an ephemeral triploid tissue derived after fertilization of the diploid central cell with a haploid sperm cell. In an effort to identify novel imprinted genes in Arabidopsis thaliana, we generated deep sequencing RNA profiles of F1 hybrid seeds derived after reciprocal crosses of Arabidopsis Col-0 and Bur-0 accessions. Using polymorphic sites to quantify allele-specific expression levels, we could identify more than 60 genes with potential parent-of-origin specific expression. By analyzing the distribution of DNA methylation and epigenetic marks established by Polycomb group (PcG) proteins using publicly available datasets, we suggest that for maternally expressed genes (MEGs) repression of the paternally inherited alleles largely depends on DNA methylation or PcG-mediated repression, whereas repression of the maternal alleles of paternally expressed genes (PEGs) predominantly depends on PcG proteins. While maternal alleles of MEGs are also targeted by PcG proteins, such targeting does not cause complete repression. Candidate MEGs and PEGs are enriched for cis-proximal transposons, suggesting that transposons might be a driving force for the evolution of imprinted genes in Arabidopsis. In addition, we find that MEGs and PEGs are significantly faster evolving when compared to other genes in the genome. In contrast to the predominant location of mammalian imprinted genes in clusters, cluster formation was only detected for few MEGs and PEGs, suggesting that clustering is not a major requirement for imprinted gene regulation in Arabidopsis

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts