Replication Study: Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis

As part of the Reproducibility Project: Cancer Biology we published a Registered Report (Fiering et al., 2015) that described how we intended to replicate selected experiments from the paper ‘Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis’ (Goetz et al., 2011). Here we report the results. Primary mouse embryonic fibroblasts (pMEFs) expressing caveolin 1 (Cav1WT) demonstrated increased extracellular matrix remodeling in vitro compared to Cav1 deficient (Cav1KO) pMEFs, similar to the original study (Goetz et al., 2011). In vivo, we found higher levels of intratumoral stroma remodeling, determined by fibronectin fiber orientation, in tumors from cancer cells co-injected with Cav1WT pMEFs compared to cancer cells only or cancer cells plus Cav1KO pMEFs, which were in the same direction as the original study (Supplemental Figure S7C; Goetz et al., 2011), but not statistically significant. Primary tumor growth was similar between conditions, like the original study (Supplemental Figure S7Ca; Goetz et al., 2011). We found metastatic burden was similar between Cav1WT and Cav1KO pMEFs, while the original study found increased metastases with Cav1WT (Figure 7C; Goetz et al., 2011); however, the duration of our in vivo experiments (45 days) were much shorter than in the study by Goetz et al. (2011) (75 days). This makes it difficult to interpret the difference between the studies as it is possible that the cells required more time to manifest the difference between treatments observed by Goetz et al. We also found a statistically significant negative correlation of intratumoral remodeling with metastatic burden, while the original study found a statistically significant positive correlation (Figure 7Cd; Goetz et al., 2011), but again there were differences between the studies in terms of the duration of the metastasis studies and the imaging approaches that could have impacted the outcomes. Finally, we report meta-analyses for each result

Low seroprevalence of COVID-19 in Lao PDR, late 2020

Background In 2020 Lao PDR had low reported COVID-19 cases but it was unclear whether this masked silent transmission. A seroprevalence study was done August - September 2020 to determine SARS-CoV-2 exposure. Methods Participants were from the general community (n=2433) or healthcare workers (n=666) in five provinces and bat/wildlife contacts (n=74) were from Vientiane province. ELISAs detected anti- SARS-CoV-2 Nucleoprotein (N; n=3173 tested) and Spike (S; n=1417 tested) antibodies. Double-positive samples were checked by IgM/IgG rapid tests. Controls were confirmed COVID-19 cases (n=15) and pre-COVID-19 samples (n=265). Seroprevalence for the general community was weighted to account for complex survey sample design, age and sex. Findings In pre-COVID-19 samples, 5·3%, [95% CI=3·1-8·7%] were anti-N antibody single-positive and 1·1% [0·3-3·5%] were anti-S antibody single positive. None were double positive. Anti-N and anti-S antibodies were detected in 5·2% [4·2-6·5%] and 2·1% [1·1-3·9%] of the general community, 2·0% [1·1-3·3%] and 1·4% [0·5-3·7%] of healthcare workers and 20·3% [12·6-31·0%] and 6·8% [2·8-15·3%] of bat/wildlife contacts. 0·1% [0·02-0·3%] were double positive for anti-N and anti-S antibodies (rapid test negative). Interpretation We find no evidence for significant SARS-CoV-2 circulation in Lao PDR before September 2020. This likely results from early decisive measures taken by the government, social behavior, and low population density. High anti-N /low anti-S seroprevalence in bat/wildlife contacts may indicate exposure to cross-reactive animal coronaviruses with threat of emerging novel viruses. Funding Agence Française de Développement. Additional; Institut Pasteur du Laos, Institute Pasteur, Paris and Luxembourg Ministry of Foreign and European Affairs (“PaReCIDS II”)

Community-developed checklists for publishing images and image analysis

Images document scientific discoveries and are prevalent in modern biomedical research. Microscopy imaging in particular is currently undergoing rapid technological advancements. However for scientists wishing to publish the obtained images and image analyses results, there are to date no unified guidelines. Consequently, microscopy images and image data in publications may be unclear or difficult to interpret. Here we present community-developed checklists for preparing light microscopy images and image analysis for publications. These checklists offer authors, readers, and publishers key recommendations for image formatting and annotation, color selection, data availability, and for reporting image analysis workflows. The goal of our guidelines is to increase the clarity and reproducibility of image figures and thereby heighten the quality of microscopy data is in publications.Comment: 28 pages, 8 Figures, 3 Supplmentary Figures, Manuscript, Essential recommendations for publication of microscopy image dat

HTLV-I tax interactions with the NF-kBIkB regulators of transcription

The human T cell leukemia virus type I (HTLV-I) is the etiological agent of adult T cell leukemia. The oncogenic potential of HTLV-I resides in the viral Tax protein which behaves as a strong transcriptional activator of viral gene expression. Tax is also capable of trans-activating numerous growth regulatory genes by an indirect mechanism. One of the targets of Tax protein is the NF-$kappa$B/I$kappa$B family of transcriptional regulators. The objective of this thesis was to characterize the molecular mechanisms by which Tax interacts with the NF-$kappa$B/I$kappa$B proteins to initiate aberrant gene expression. HTLV-I infected and Tax expressing T cell models were initially used to demonstrate a constitutive level of NF-$kappa$B DNA binding activity and increased NF-$kappa$B-dependent transcriptional activity. NFKB2 and c-Rel subunits were overexpressed in these cells and constituted the majority of the NF-$kappa$B/Rel heterodimers binding to DNA. A reduction in NF-$kappa$B p65 nuclear expression and DNA binding activity was also observed. Importantly, a novel complex composed of NFKB2 p100 and Tax was detected in HTLV-I infected cells, thus demonstrating physical interaction between viral and cellular proteins. These in vivo observations were confirmed in Tax-NF-$kappa$B co-transfection studies which demonstrated a Tax-dependent correlation between expression of NFKB2 p100 and processing to p52, induction of c-Rel, and trans-activation of NF-$kappa$B-mediated gene expression. A co-transfection-immunofluorescence assay provided additional support for direct Tax-NF-$kappa$B physical interactions by demonstrating the ability of p100, p105 and p52 to modify the intracellular localization of Tax. The possibility that constitutive NF-$kappa$B activity resulted from a Tax-mediated effect on $rm I kappa B alpha$ function was also examined. Constitutive phosphorylation and increased turnover of I$kappa$Ba were observed in HTLV-I infected and Tax expressin

Témoignage et fiction

International audienc

Research Data Management Community Guidelines and Tools for Reporting and Reproducibility in Light Microscopy

This talk was presented on 12/2/2022 by Judith Lacoste and Caterina Strambio-De-Castillia during a visit of representatives of BioImaging North America (BINA; https://www.bioimagingnorthamerica.org/) and QUality Assessment and REProducibility for Images and Instrument in Light Microscopy (QUAREP-LiMi; https://quarep.org/) to the National Institute of Science and Technology (NIST).</p

Anonymous Theology and Pseudonymous Christology

Translation of ‘Théologie anonyme et christologie pseudonyme.' By Jean-Yves Lacoste. Originally published in his Narnia, monde théologique. Geneva: Ad Solem, 2005