The fables of pity: Rousseau, Mandeville and the animal-fable

Copyright @ 2012 Edinburgh University PressPrompted by Derrida’s work on the animal-fable in eighteenth-century debates about political power, this article examines the role played by the fiction of the animal in thinking of pity as either a natural virtue (in Rousseau’s Second Discourse) or as a natural passion (in Mandeville’s The Fable of the Bees). The war of fables between Rousseau and Mandeville – and their hostile reception by Samuel Johnson and Adam Smith – reinforce that the animal-fable illustrates not so much the proper of man as the possibilities and limitations of a moral philosophy that is unable to address the political realities of the state

Immune responses during COVID-19 infection

Over the past 16 years, three coronaviruses (CoVs), severe acute respiratory syndrome CoV (SARS-CoV) in 2002, Middle East respiratory syndrome CoV (MERS-CoV) in 2012 and 2015, and SARS-CoV-2 in 2020, have been causing severe and fatal human epidemics. The unpredictability of coronavirus disease-19 (COVID-19) poses a major burden on health care and economic systems across the world. This is caused by the paucity of in-depth knowledge of the risk factors for severe COVID-19, insufficient diagnostic tools for the detection of SARS-CoV-2, as well as the absence of specific and effective drug treatments. While protective humoral and cellular immune responses are usually mounted against these betacoronaviruses, immune responses to SARS-CoV2 sometimes derail towards inflammatory tissue damage, leading to rapid admissions to intensive care units. The lack of knowledge on mechanisms that tilt the balance between these two opposite outcomes poses major threats to many ongoing clinical trials dealing with immunostimulatory or immunoregulatory therapeutics. This review will discuss innate and cognate immune responses underlying protective or deleterious immune reactions against these pathogenic coronaviruses

Data submission and curation for caArray, a standard based microarray data repository system

caArray is an open-source, open development, web and programmatically accessible array data management system developed at National Cancer Institute. It was developed to support the exchange of array data across the Cancer Biomedical Informatics Grid (caBIG™), a collaborative information network that connect scientists and practitioners through a shareable and interoperable infrastructure to share data and knowledge. caArray adopts a federated model of local installations, in which data deposited are shareable across caBIG™. 

Comprehensive in annotation yet easy to use has always been a challenge to any data repository system. To alleviate this difficulty, caArray accepts data upload using the MAGE-TAB, a spreadsheet-based format for annotating and communicating microarray data in a MIAME-compliant fashion ("http://www.mged.org/mage-tab":http://www.mged.org/mage-tab). MAGE-TAB is built on community standards – MAGE, MIAME, and Ontology. The components and work flow of MAGE-TAB files are organized in such a way which is already familiar to bench scientists and thus minimize the time and frustration of reorganizing their data before submission. The MAGE-TAB files are also structured to be machine readable so that they can be easily parsed into database. Users can control public access to experiment- and sample-level data and can create collaboration groups to support data exchange among a defined set of partners. 

All data submitted to caArray at NCI will go through strict curation by a group of scientists against these standards to make sure that the data are correctly annotated using proper controlled vocabulary terms and all required information are provided. Two of mostly used ontology sources are MGED ontology ("http://mged.sourceforge.net/ontologies/MGEDontology.php":http://mged.sourceforge.net/ontologies/MGEDontology.php) and NCI thesaurus ("http://nciterms.nci.nih.gov/NCIBrowser/Dictionary.do":http://nciterms.nci.nih.gov/NCIBrowser/Dictionary.do). The purpose of data curation is to ensure easy comparison of results from different labs and unambiguous report of results. 

Data will also undergo automatic validation process before parsed into database, in which minimum information requirement and data consistency with the array designs are checked. Files with error found during validation are flagged with error message. Curators will re-examine those files and make necessary corrections before re-load the files. The iteration repeats until files are validated successfully. Data are then imported into the system and ready for access through the portal or through API. Interested parties are encouraged to review the installation package, documentation, and source code available from "http://caarray.nci.nih.gov":http://caarray.nci.nih.gov

Immunocluster provides a computational framework for the nonspecialist to profile high-dimensional cytometry data

High-dimensional cytometry is an innovative tool for immune monitoring in health and disease, and it has provided novel insight into the underlying biology as well as biomarkers for a variety of diseases. However, the analysis of large multiparametric datasets usually requires specialist computational knowledge. Here, we describe ImmunoCluster (https://github.com/ kordastilab/ImmunoCluster), an R package for immune profiling cellular heterogeneity in highdimensional liquid and imaging mass cytometry, and flow cytometry data, designed to facilitate computational analysis by a nonspecialist. The analysis framework implemented within ImmunoCluster is readily scalable to millions of cells and provides a variety of visualization and analytical approaches, as well as a rich array of plotting tools that can be tailored to users’ needs. The protocol consists of three core computational stages: (1) data import and quality control; (2) dimensionality reduction and unsupervised clustering; and (3) annotation and differential testing, all contained within an R-based open-source framework

Lysosomes in iron metabolism, ageing and apoptosis

The lysosomal compartment is essential for a variety of cellular functions, including the normal turnover of most long-lived proteins and all organelles. The compartment consists of numerous acidic vesicles (pH ∼4 to 5) that constantly fuse and divide. It receives a large number of hydrolases (∼50) from the trans-Golgi network, and substrates from both the cells’ outside (heterophagy) and inside (autophagy). Many macromolecules contain iron that gives rise to an iron-rich environment in lysosomes that recently have degraded such macromolecules. Iron-rich lysosomes are sensitive to oxidative stress, while ‘resting’ lysosomes, which have not recently participated in autophagic events, are not. The magnitude of oxidative stress determines the degree of lysosomal destabilization and, consequently, whether arrested growth, reparative autophagy, apoptosis, or necrosis will follow. Heterophagy is the first step in the process by which immunocompetent cells modify antigens and produce antibodies, while exocytosis of lysosomal enzymes may promote tumor invasion, angiogenesis, and metastasis. Apart from being an essential turnover process, autophagy is also a mechanism by which cells will be able to sustain temporary starvation and rid themselves of intracellular organisms that have invaded, although some pathogens have evolved mechanisms to prevent their destruction. Mutated lysosomal enzymes are the underlying cause of a number of lysosomal storage diseases involving the accumulation of materials that would be the substrate for the corresponding hydrolases, were they not defective. The normal, low-level diffusion of hydrogen peroxide into iron-rich lysosomes causes the slow formation of lipofuscin in long-lived postmitotic cells, where it occupies a substantial part of the lysosomal compartment at the end of the life span. This seems to result in the diversion of newly produced lysosomal enzymes away from autophagosomes, leading to the accumulation of malfunctioning mitochondria and proteins with consequent cellular dysfunction. If autophagy were a perfect turnover process, postmitotic ageing and several age-related neurodegenerative diseases would, perhaps, not take place