"Tonga" : A Novel Toolbox for Straightforward Bioimage Analysis

Techniques to acquire and analyze biological images are central to life science. However, the workflow downstream of imaging can be complex and involve several tools, leading to creation of very specialized scripts and pipelines that are difficult to reproduce by other users. Although many commercial and open-source software are available, non-expert users are often challenged by a knowledge gap in setting up analysis pipelines and selecting correct tools for extracting data from images. Moreover, a significant share of everyday image analysis requires simple tools, such as precise segmentation, cell counting, and recording of fluorescent intensities. Hence, there is a need for user-friendly platforms for everyday image analysis that do not require extensive prior knowledge on bioimage analysis or coding. We set out to create a bioimage analysis software that has a straightforward interface and covers common analysis tasks such as object segmentation and analysis, in a practical, reproducible, and modular fashion. We envision our software being useful for analysis of cultured cells, histological sections, and high-content data.Peer reviewe

Suoliston kantasolut

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Laminin alpha 5 regulates mammary gland remodeling through luminal cell differentiation and Wnt4-mediated epithelial crosstalk

Epithelial attachment to the basement membrane (BM) is essential for mammary gland development, yet the exact roles of specific BM components remain unclear. Here, we show that Laminin alpha 5 (Lama5) expression specifically in the luminal epithelial cells is necessary for normal mammary gland growth during puberty, and for alveologenesis during pregnancy. Lama5 loss in the keratin 8-expressing cells results in reduced frequency and differentiation of hormone receptor expressing (HR+) luminal cells. Consequently, Wnt4-mediated crosstalk between HR+ luminal cells and basal epithelial cells is compromised during gland remodeling, and results in defective epithelial growth. The effects of Lama5 deletion on gland growth and branching can be rescued by Wnt4 supplementation in the in vitro model of branching morphogenesis. Our results reveal a surprising role for BM-protein expression in the luminal mammary epithelial cells, and highlight the function of Lama5 in mammary gland remodeling and luminal differentiation.Peer reviewe

Asymmetric apportioning of aged mitochondria between daughter cells is required for stemness

By dividing asymmetrically, stem cells can generate two daughter cells with distinct fates. However, evidence is limited in mammalian systems for the selective apportioning of subcellular contents between daughters. We followed the fates of old and young organelles during the division of human mammary stemlike cells and found that such cells apportion aged mitochondria asymmetrically between daughter cells. Daughter cells that received fewer old mitochondria maintained stem cell traits. Inhibition of mitochondrial fission disrupted both the age-dependent subcellular localization and segregation of mitochondria and caused loss of stem cell properties in the progeny cells. Hence, mechanisms exist for mammalian stemlike cells to asymmetrically sort aged and young mitochondria, and these are important for maintaining stemness properties.National Science Foundation (U.S.). Long-Term Ecological Research Program (DEB-8811884)National Science Foundation (U.S.). Long-Term Ecological Research Program (DEB-9411972)National Science Foundation (U.S.). Long-Term Ecological Research Program (DEB-0080382)National Science Foundation (U.S.). Long-Term Ecological Research Program (DEB-0620652)National Science Foundation (U.S.). Long-Term Ecological Research Program (DEB-1234162)National Science Foundation (U.S.). (Biocomplexity Coupled Biogeocemhical Cycles. DEB-0322057)National Science Foundation (U.S.). Long-Term Research in Environmental Biology (DEB-0716587)National Science Foundation (U.S.). Long-Term Research in Environmental Biology (DEB-1242531)National Science Foundation (U.S.). Long-Term Research in Ecosystem Sciences (DEB-1120064)United States. Dept. of Energy. Program for Ecoysystem Research (DE-FG02-96ER62291)United States. Dept. of Energy. Office of Biological and Environmental Research. National Institute for Climatic Change Research (Grant DE-FC02-06ER64158

Distribution and abundance of the American comb jelly (Mnemiopsis leidyi) - a rapid invasion to the northern Baltic Sea during 2007

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WNT2 activation through proximal germline deletion predisposes to small intestinal neuroendocrine tumors and intestinal adenocarcinomas

Many hereditary cancer syndromes are associated with an increased risk of small and large intestinal adenocarcinomas. However, conditions bearing a high risk to both adenocarcinomas and neuroendocrine tumors are yet to be described.We studied a family with 16 individuals in four generations affected by a wide spectrum of intestinal tumors, including hyperplastic polyps, adenomas, small intestinal neuroendocrine tumors, and colorectal and small intestinal adenocarcinomas.To assess the genetic susceptibility and understand the novel phenotype, we utilized multiple molecular methods, including whole genome sequencing, RNA sequencing, single cell sequencing, RNA in situ hybridization and organoid culture.We detected a heterozygous deletion at the cystic fibrosis locus (7q31.2) perfectly segregating with the intestinal tumor predisposition in the family. The deletion removes a topologically associating domain border between CFTR and WNT2, aberrantly activating WNT2 in the intestinal epithelium. These consequences suggest that the deletion predisposes to small intestinal neuroendocrine tumors and small and large intestinal adenocarcinomas, and reveals the broad tumorigenic effects of aberrant WNT activation in the human intestine.Peer reviewe