Identification and characterization of a spontaneous ovarian carcinoma in Lewis rats

<p>Abstract</p> <p>Background</p> <p>Ovarian carcinoma is the fourth most common cause of death from cancer in women. Limited progress has been made toward improving the survival rate of patients with this disease in part because of the lack of a good animal model. We present here a model of spontaneous ovarian carcinoma arising in a normal Lewis rat.</p> <p>Methods</p> <p>A spontaneously occurring tumor of the left ovary was found in a normal Lewis rat during necropsy, which was sectioned for histological examination and placed into single cell suspension. Tumor cells were passaged <it>in vivo </it>by intraperitoneal injection into immunocompetent Lewis rats, and <it>in vitro </it>culture resulted in generation of a cell line. Tumor cells were examined by flow cytometry for expression of estrogen receptor α, progesterone receptor, androgen receptor, her-2/neu, epithelial cell adhesion molecule, and CA125. β-catenin expression and cellular localization was assessed by immunocytochemistry. RNA was harvested for gene expression profiling and studying the expression of cytokines.</p> <p>Results</p> <p>The tumor, designated FNAR, could be serially transplanted into Lewis rats and propagated as a cell line <it>in vitro</it>, maintaining the properties of the original tumor. The FNAR cells displayed striking morphologic similarities to human ovarian carcinoma, resembling the endometrioid carcinoma subtype of surface epithelial neoplasms. The cells expressed estrogen receptor α, progesterone receptor, androgen receptor, her-2/neu, epithelial cell adhesion molecule, CA125, and nuclear β-catenin. A gene expression profile showed upregulation of a number of genes that are also upregulated in human ovarian carcinoma.</p> <p>Conclusion</p> <p>This reliable model of ovarian carcinoma should be helpful in better understanding the biology of the disease as well as the development of novel treatment strategies.</p

Bone Marrow Transplantation Results in Human Donor Blood Cells Acquiring and Displaying Mouse Recipient Class I MHC and CD45 Antigens on Their Surface

Background: Mouse models of human disease are invaluable for determining the differentiation ability and functional capacity of stem cells. The best example is bone marrow transplants for studies of hematopoietic stem cells. For organ studies, the interpretation of the data can be difficult as transdifferentiation, cell fusion or surface antigen transfer (trogocytosis) can be misinterpreted as differentiation. These events have not been investigated in hematopoietic stem cell transplant models. Methodology/Principal Findings: In this study we investigated fusion and trogocytosis involving blood cells during bone marrow transplantation using a xenograft model. We report that using a standard SCID repopulating assay almost 100 % of the human donor cells appear as hybrid blood cells containing both mouse and human surface antigens. Conclusion/Significance: Hybrid cells are not the result of cell-cell fusion events but appear to be due to efficient surface antigen transfer, a process referred to as trogocytosis. Antigen transfer appears to be non-random and includes all donor cells regardless of sub-type. We also demonstrate that irradiation preconditioning enhances the frequency of hybrid cell

The Contingency of Success: Deep Impact's Planet Hunt

No abstract availabl

Overview of the Mars 2020 mission micro-XRF instrument PIXL

PIXL (Planetary Instrument for X-ray Lithochem.) is a micro-focus X-ray fluorescence instrument for examg. fine scale chem. variations in rocks and soils on planetary surfaces. Selected for flight on the Mars 2020 rover science payload, PIXL can measure elemental chem. of tiny features obsd. in rocks, such as individual sand grains, veinlets, cements, concretions and crystals. The PIXL sensor head is mounted on the turret at the end of the Mars 2020 rover arm. It combines a novel, 28 kV power supply (S. Battel, University of Michigan) with a newly developed side-window, grounded-cathode x-ray tube (Moxtek), and a polycapillary xray optic (XOS) to generate a 120 mm diam. x-ray beam that is rastered over a 24 mm x 24 mm field of view. Two SDD detectors are used to collect the fluoresced spectra and an optical fiducial subsystem is used to image rock morphol., guide placement of PIXL, and det. the x-ray beam location on the targeted surface. The overall PIXL design, performance and operational concepts will be presented, along with a summary of development test results

Global, regional, and national trends in under-5 mortality between 1990 and 2019 with scenario-based projections until 2030: a systematic analysis by the UN Inter-agency Group for Child Mortality Estimation

Background The Sustainable Development Goals (SDGs), set in 2015 by the UN General Assembly, call for all countries to reach an under-5 mortality rate (U5MR) of at least as low as 25 deaths per 1000 livebirths and a neonatal mortality rate (NMR) of at least as low as 12 deaths per 1000 livebirths by 2030. We estimated levels and trends in under-5 mortality for 195 countries from 1990 to 2019, and conducted scenario-based projections of the U5MR and NMR from 2020 to 2030 to assess country progress in, and potential for, reaching SDG targets on child survival and the potential under-5 and neonatal deaths over the next decade. Methods Levels and trends in under-5 mortality are based on the UN Inter-agency Group for Child Mortality Estimation (UN IGME) database on under-5 mortality, which contains around 18 000 country-year datapoints for 195 countries—nearly 10 000 of those datapoints since 1990. The database includes nationally representative mortality data from vital registration systems, sample registration systems, population censuses, and household surveys. As with previous sets of national UN IGME estimates, a Bayesian B-spline bias-reduction model (B3) that considers the systematic biases associated with the different data source types was fitted to these data to generate estimates of under-5 (age 0–4 years) mortality with uncertainty intervals for 1990–2019 for all countries. Levels and trends in the neonatal mortality rate (0–27 days) are modelled separately as the log ratio of the neonatal mortality rate to the under-5 mortality rate using a Bayesian model. Estimated mortality rates are combined with livebirths data to calculate the number of under-5 and neonatal deaths. To assess the regional and global burden of under-5 deaths in the present decade and progress towards SDG targets, we constructed several scenario-based projections of under-5 mortality from 2020 to 2030 and estimated national, regional, and global under-5 mortality trends up to 2030 for each scenario. Findings The global U5MR decreased by 59% (90% uncertainty interval [UI] 56–61) from 93·0 (91·7–94·5) deaths per 1000 livebirths in 1990 to 37·7 (36·1–40·8) in 2019, while the annual number of global under-5 deaths declined from 12·5 (12·3–12·7) million in 1990 to 5·2 (5·0–5·6) million in 2019—a 58% (55–60) reduction. The global NMR decreased by 52% (90% UI 48–55) from 36·6 (35·6–37·8) deaths per 1000 livebirths in 1990, to 17·5 (16·6–19·0) in 2019, and the annual number of global neonatal deaths declined from 5·0 (4·9–5·2) million in 1990, to 2·4 (2·3–2·7) million in 2019, a 51% (47–54) reduction. As of 2019, 122 of 195 countries have achieved the SDG U5MR target, and 20 countries are on track to achieve the target by 2030, while 53 will need to accelerate progress to meet the target by 2030. 116 countries have reached the SDG NMR target with 16 on track, leaving 63 at risk of missing the target. If current trends continue, 48·1 million under-5 deaths are projected to occur between 2020 and 2030, almost half of them projected to occur during the neonatal period. If all countries met the SDG target on under-5 mortality, 11 million under-5 deaths could be averted between 2020 and 2030. Interpretation As a result of effective global health initiatives, millions of child deaths have been prevented since 1990. However, the task of ending all preventable child deaths is not done and millions more deaths could be averted by meeting international targets. Geographical and economic variation demonstrate the possibility of even lower mortality rates for children under age 5 years and point to the regions and countries with highest mortality rates and in greatest need of resources and action. Funding Bill & Melinda Gates Foundation, US Agency for International Development

Suspendable Hydrogel Nanovials for Massively Parallel Single-Cell Functional Analysis and Sorting

Techniques to analyze and sort single cells based on functional outputs, such as secreted products, have the potential to transform our understanding of cellular biology as well as accelerate the development of next-generation cell and antibody therapies. However, secreted molecules rapidly diffuse away from cells, and analysis of these products requires specialized equipment and expertise to compartmentalize individual cells and capture their secretions. Herein, we describe methods to fabricate hydrogel-based chemically functionalized microcontainers, which we call nanovials, and demonstrate their use for sorting single viable cells based on their secreted products at high-throughput using only commonly accessible laboratory infrastructure. These nanovials act as solid supports that facilitate attachment of a variety of adherent and suspension cell types, partition uniform aqueous compartments, and capture secreted proteins. Solutions can be exchanged around nanovials to perform fluorescence immunoassays on secreted proteins. Using this platform and commercial flow sorters, we demonstrate high-throughput screening of stably and transiently transfected producer cells based on relative IgG production. Chinese hamster ovary cells sorted based on IgG production regrew and maintained a high secretion phenotype over at least a week, yielding &gt;40% increase in bulk IgG production rates. We also sorted hybridomas and B lymphocytes based on antigen-specific antibody production. Hybridoma cells secreting an antihen egg lysozyme antibody were recovered from background cells, enriching a population of ∼4% prevalence to &gt;90% following sorting. Leveraging the high-speed sorting capabilities of standard sorters, we sorted &gt;1 million events in &lt;1 h. IgG secreting mouse B cells were also sorted and enriched based on antigen-specific binding. Successful sorting of antibody-secreting B cells combined with the ability to perform single-cell RT-PCR to recover sequence information suggests the potential to perform antibody discovery workflows. The reported nanovials can be easily stored and distributed among researchers, democratizing access to high-throughput functional cell screening