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

Die Strandaster-Seidenbiene Colletes halophilus Verhoeff, 1944 (Hymenoptera: Colletidae) ist weit verbreitet an der Ostseeküste von Dänemark und Deutschland

The Sea Aster mining bee Colletes halophilus Verhoeff, 1944 is known as an endemic of the western European coasts of the Atlantic and the North Sea. The species has specific habitat requirements and is restricted to coastal habitats with populations of the Sea Aster (Tripolium pannonicum), its preferred host plant. Due to the late summer activity of adults and habitat specialisation, this solitary bee species is easily overlooked. In 2019, C. halophilus was first found at the Baltic Sea coast of the island of Fyn (Denmark), 2020 on the island of Rügen (Mecklenburg-Vorpommern, Germany) and in 2021 in Sehlendorf (Schleswig-Holstein, Germany), demonstrating that the species is far more widespread and also occurring along the more continental Western Baltic Sea coast and Kattegat. Targeted sampling in 2022 revealed that C. halophilus is now present in most of the potentially suitable coastal habitats in Schleswig-Holstein and at least in some parts of Mecklenburg-Vorpommern. We here present data on the currently known distribution of C. halophilus along the Baltic Sea coast of Denmark and Germany and discuss hypotheses of a potential recent range extension.Die Strandaster-Seidenbiene Colletes halophilus Verhoeff, 1944 ist ein Endemit der Atlantik- und Nordseeküste Westeuropas und aufgrund ihrer spezifischen Habitatansprüche an Küstenbiotope mit Vorkommen der Strandaster (Tripolium pannonicum) als bevorzugter Futterpflanze gebunden. Aufgrund der späten Flugzeit und ihrer Habitatspezifität kann die Art leicht übersehen werden. Durch Funde der Art auf der Insel Fünen (DK) 2019, Rügen (MV) 2020 und Sehlendorf (SH) 2021 wurde deutlich, dass die Art deutlich weiter verbreitet ist und auch im Bereich der kontinentaleren Ostseeküste vorkommt. Durch gezielte Nachsuche im Jahr 2022 konnte die Art in den meisten potentiell geeignet erscheinenden Küstenhabitaten in Schleswig-Holstein und einigen Gebieten in Mecklenburg-Vorpommern festgestellt werden. Der aktuelle Kenntnisstand zur Verbreitung von C. halophilus an der Ostseeküste wird vorgestellt und Hypothesen einer möglichen rezenten Aus- breitung der Art werden diskutiert

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

Learning hand in hand: Engaging in research-practice partnerships to advance developmental science.

Developmental science research often involves research questions developed by academic teams, which are tested within community or educational settings. In this piece, we outline the importance of research-practice partnerships, which involve both research and practice-based partners collaborating at each stage of the research process. We articulate challenges and benefits of these partnerships for developmental science research, identify relevant research frameworks that may inform these partnerships, and provide an example of an ongoing research-practice partnership

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

A comprehensive assessment of somatic mutation detection in cancer using whole-genome sequencing.

As whole-genome sequencing for cancer genome analysis becomes a clinical tool, a full understanding of the variables affecting sequencing analysis output is required. Here using tumour-normal sample pairs from two different types of cancer, chronic lymphocytic leukaemia and medulloblastoma, we conduct a benchmarking exercise within the context of the International Cancer Genome Consortium. We compare sequencing methods, analysis pipelines and validation methods. We show that using PCR-free methods and increasing sequencing depth to ∼ 100 × shows benefits, as long as the tumour:control coverage ratio remains balanced. We observe widely varying mutation call rates and low concordance among analysis pipelines, reflecting the artefact-prone nature of the raw data and lack of standards for dealing with the artefacts. However, we show that, using the benchmark mutation set we have created, many issues are in fact easy to remedy and have an immediate positive impact on mutation detection accuracy.We thank the DKFZ Genomics and Proteomics Core Facility and the OICR Genome Technologies Platform for provision of sequencing services. Financial support was provided by the consortium projects READNA under grant agreement FP7 Health-F4-2008-201418, ESGI under grant agreement 262055, GEUVADIS under grant agreement 261123 of the European Commission Framework Programme 7, ICGC-CLL through the Spanish Ministry of Science and Innovation (MICINN), the Instituto de Salud Carlos III (ISCIII) and the Generalitat de Catalunya. Additional financial support was provided by the PedBrain Tumor Project contributing to the International Cancer Genome Consortium, funded by German Cancer Aid (109252) and by the German Federal Ministry of Education and Research (BMBF, grants #01KU1201A, MedSys #0315416C and NGFNplus #01GS0883; the Ontario Institute for Cancer Research to PCB and JDM through funding provided by the Government of Ontario, Ministry of Research and Innovation; Genome Canada; the Canada Foundation for Innovation and Prostate Cancer Canada with funding from the Movember Foundation (PCB). PCB was also supported by a Terry Fox Research Institute New Investigator Award, a CIHR New Investigator Award and a Genome Canada Large-Scale Applied Project Contract. The Synergie Lyon Cancer platform has received support from the French National Institute of Cancer (INCa) and from the ABS4NGS ANR project (ANR-11-BINF-0001-06). The ICGC RIKEN study was supported partially by RIKEN President’s Fund 2011, and the supercomputing resource for the RIKEN study was provided by the Human Genome Center, University of Tokyo. MDE, LB, AGL and CLA were supported by Cancer Research UK, the University of Cambridge and Hutchison-Whampoa Limited. SD is supported by the Torres Quevedo subprogram (MI CINN) under grant agreement PTQ-12-05391. EH is supported by the Research Council of Norway under grant agreements 221580 and 218241 and by the Norwegian Cancer Society under grant agreement 71220-PR-2006-0433. Very special thanks go to Jennifer Jennings for administrating the activity of the ICGC Verification Working Group and Anna Borrell for administrative support.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms1000

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