Parental genetic shaping and parental environmental shaping

Analytic philosophers tend to agree that intentional parental genetic shaping and intentional parental environmental shaping for the same feature are, normatively, on a par. I challenge this view by advancing a novel argument, grounded in the value of fair relationships between parents and children: Parental genetic shaping is morally objectionable because it unjustifiably exacerbates the asymmetry between parent and child with respect to the voluntariness of their entrance into the parent–child relationship. Parental genetic shaping is, for this reason, different from and more objectionable than parental environmental shaping. I introduce a distinction between procreative decisions one makes qua mere procreator—that is, without the intention to rear the resulting child—and procreative decisions one makes qua procreator-and-future childrearer. Genetic shaping is objectionable when undertaken in the latter capacity: Both selection and enhancement are objectionable because they introduce an unnecessary and avoidable inequality in the parent–child relationship; in the case of enhancement, this also results in harm to the future child

Pinpointing cell identity in time and space

Copyright © 2020 Savulescu, Jacobs, Negishi, Davignon and Mhlanga. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Mammalian cells display a broad spectrum of phenotypes, morphologies, and functional niches within biological systems. Our understanding of mechanisms at the individual cellular level, and how cells function in concert to form tissues, organs and systems, has been greatly facilitated by centuries of extensive work to classify and characterize cell types. Classic histological approaches are now complemented with advanced single-cell sequencing and spatial transcriptomics for cell identity studies. Emerging data suggests that additional levels of information should be considered, including the subcellular spatial distribution of molecules such as RNA and protein, when classifying cells. In this Perspective piece we describe the importance of integrating cell transcriptional state with tissue and subcellular spatial and temporal information for thorough characterization of cell type and state. We refer to recent studies making use of single cell RNA-seq and/or image-based cell characterization, which highlight a need for such in-depth characterization of cell populations. We also describe the advances required in experimental, imaging and analytical methods to address these questions. This Perspective concludes by framing this argument in the context of projects such as the Human Cell Atlas, and related fields of cancer research and developmental biology.info:eu-repo/semantics/publishedVersio

Parental enhancement and symmetry of power in the parent–child relationship

Many instances of parental enhancement are objectionable on egalitarian grounds because they unnecessarily amplify one kind of asymmetry of power between parents and children. Because children have full moral status, we ought to seek egalitarian relationships with them. Such relationships are compatible with asymmetries of power only to the extent to which the asymmetry is necessary for (1) advancing the child's level of advantage up to what justice requires or (2) instilling in the child morally required features. This is a ground to oppose parental enhancements whose purpose is either to merely satisfy parents' preferences or to confer on the child advantages above and beyond what the child is owed by justice

Super-resolution microscopy reveals a preformed NEMO lattice structure that is collapsed in incontinentia pigmenti

The data that support the findings of this study are available from the corresponding authors upon request.International audienceThe NF-kB pathway has critical roles in cancer, immunity and inflammatory responses. Understanding the mechanism(s) by which mutations in genes involved in the pathway cause disease has provided valuable insight into its regulation, yet many aspects remain unexplained. Several lines of evidence have led to the hypothesis that the regulatory/sensor protein NEMO acts as a biological binary switch. This hypothesis depends on the formation of a higher-order structure, which has yet to be identified using traditional molecular techniques. Here we use super-resolution microscopy to reveal the existence of higher-order NEMO lattice structures dependent on the presence of polyubiquitin chains before NF-kB activation. Such structures may permit proximity-based trans-autophosphorylation, leading to cooperative activation of the signalling cascade. We further show that NF-kB activation results in modification of these structures. Finally, we demonstrate that these structures are abrogated in cells derived from incontinentia pigmenti patients

DypFISH: Dynamic Patterned FISH to Interrogate RNA and Protein Spatial and Temporal Subcellular Distribution

Advances in single cell RNA sequencing have allowed for the identification and characterization of cellular subtypes based on quantification of the number of transcripts in each cell. However, cells may differ not only in the number of mRNA transcripts that they exhibit, but also in their spatial and temporal distribution, intrinsic to the definition of their cellular state. Here we describe DypFISH, an approach to quantitatively investigate the spatial and temporal subcellular localization of RNA and protein, by combining micropatterning of cells with fluorescence microscopy at high resolution. We introduce a range of analytical techniques for quantitatively interrogating single molecule RNA FISH data in combination with protein immunolabeling over time. Strikingly, our results show that constraining cellular architecture reduces variation in subcellular mRNA and protein distributions, allowing the characterization of their localization and dynamics with high reproducibility. Many tissues contain cells that exist in similar constrained architectures. Thus DypFISH reveals reproducible patterns of clustering, strong correlative influences of mRNA-protein localization on MTOC orientation when they are present and interdependent dynamics globally and at specific subcellular locations which can be extended to physiological systems

Cardiovascular Risk Factors, Angiographical Features and Short-Term Prognosis of Acute Coronary Syndrome in People Living with Human Immunodeficiency Virus: Results of a Retrospective Observational Multicentric Romanian Study

People living with human immunodeficiency virus have increased cardiovascular risk due to a higher prevalence of traditional and particular risk factors such as chronic inflammation, immune dysregulation, endothelial dysfunction, coagulation abnormalities and antiretroviral therapy. In developed countries, coronary artery disease has become the most frequent cardiovascular disease and an important cause of mortality in these patients. The symptomatology of an acute coronary syndrome can be atypical, and the prevalence of each type of acute coronary syndrome is reported differently. Regarding coronary artery disease severity in people living with HIV, the literature data indicates that the presence of single-vessel disease is akin to that of HIV-negative patients, and their short-term prognosis is unclear. This study aims to assess the clinical characteristics, biological parameters, angiographical features and short-term prognosis of acute coronary syndrome in a cohort of Romanian people living with human immunodeficiency virus

Interrogating RNA and protein spatial subcellular distribution in smFISH data with DypFISH

International audienceAdvances in single-cell RNA sequencing have allowed for the identification of cellular subtypes on the basis of quantification of the number of transcripts in each cell. However, cells might also differ in the spatial distribution of molecules, including RNAs. Here, we present DypFISH, an approach to quantitatively investigate the subcellular localization of RNA and protein. We introduce a range of analytical techniques to interrogate single-molecule RNA fluorescence in situ hybridization (smFISH) data in combination with protein immunolabeling. DypFISH is suited to study patterns of clustering of molecules, the association of mRNA-protein subcellular localization with microtubule organizing center orientation, and interdependence of mRNA-protein spatial distributions. We showcase how our analytical tools can achieve biological insights by utilizing cell micropatterning to constrain cellular architecture, which leads to reduction in subcellular mRNA distribution variation, allowing for the characterization of their localization patterns. Furthermore, we show that our method can be applied to physiological systems such as skeletal muscle fibers