Beyond advertising: New infrastructures for publishing integrated research objects

ABSTRACT: Moving beyond static text and illustrations is a central challenge for scientific publishing in the 21st century. As early as 1995, Donoho and Buckheit paraphrased John Claerbout that “an article about [a] computational result is advertising, not scholarship. The actual scholarship is the full software environment, code and data, that produced the result” [1]. Awareness of this problem has only grown over the last 25 years; nonetheless, scientific publishing infrastructures remain remarkably resistant to change [2]. Even as these infrastructures have largely stagnated, the internet has ushered in a transition “from the wet lab to the web lab” [3]. New expectations have emerged in this shift, but these expectations must play against the reality of currently available infrastructures and associated sociological pressures. Here, we compare current scientific publishing norms against those associated with online content more broadly, and we argue that meeting the “Claerbout challenge” of providing the full software environment, code, and data supporting a scientific result will require open infrastructure development to create environments for authoring, reviewing, and accessing interactive research objects

Stepwise Maturation of Lytic Granules during Differentiation and Activation of Human CD8+ T Lymphocytes

During differentiation, cytotoxic T lymphocytes (CTL) acquire their killing potential through the biogenesis and maturation of lytic granules that are secreted upon target cell recognition. How lytic granule load in lytic molecules evolves during CTL differentiation and which subsets of lytic granules are secreted following activation remains to be investigated. We set up a flow cytometry approach to analyze single lytic granules isolated from primary human CTL according to their size and molecular content. During CTL in vitro differentiation, a relatively homogeneous population of lytic granules appeared through the progressive loading of Granzyme B, Perforin and Granzyme A within LAMP1+ lysosomes. PMA/ionomycin-induced lytic granule exocytosis was preceded by a rapid association of the docking molecule Rab27a to approximately half of the lytic granules. Activated CTL were found to limit exocytosis by sparing lytic granules including some associated to Rab27a. Our study provides a quantification of key steps of lytic granule biogenesis and highlights the potential of flow cytometry to study organelle composition and dynamics

NeuroLibre : A preprint server for full-fledged reproducible neuroscience

NeuroLibre is a preprint server for neuroscience Jupyter Books, blending code, visualization and narrative text into one document. NeuroLibre archives the environment, code and data and also implements a technical review to ensure readers can reproduce the work. NeuroLibre offers an online platform where readers can reproduce or modify each preprint from a web browser, without any installation required. We hope that NeuroLibre will contribute to usher the research community in a new area of open and reproducible neuroscience. The preprint server is built with open source components, and can be freely adapted to meet the needs of other communities in the future as well

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PAM, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and pArg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM(-/-) patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors