IL-2 Mediates CD4+ T Cell Help in the Breakdown of Memory-Like CD8+ T Cell Tolerance under Lymphopenic Conditions

Background: Lymphopenia results in the proliferation and differentiation of naïve T cells into memory-like cells in the apparent absence of antigenic stimulation. This response, at least in part due to a greater availability of cytokines, is thought to promote anti-self responses. Although potentially autoreactive memory-like CD8 + T cells generated in a lymphopenic environment are subject to the mechanisms of peripheral tolerance, they can induce autoimmunity in the presence of antigen-specific memory-like CD4 + T helper cells. Methodology/Principal Findings: Here, we studied the mechanisms underlying CD4 help under lymphopenic conditions in transgenic mice expressing a model antigen in the beta cells of the pancreas. Surprisingly, we found that the self-reactivity mediated by the cooperation of memory-like CD8 + and CD4 + T cells was not abrogated by CD40L blockade. In contrast, treatment with anti-IL-2 antibodies inhibited the onset of autoimmunity. IL-2 neutralization prevented the CD4-mediated differentiation of memory-like CD8 + T cells into pathogenic effectors in response to self-antigen cross-presentation. Furthermore, in the absence of helper cells, induction of IL-2 signaling by an IL-2 immune complex was sufficient to promote memory-like CD8 + T cell self-reactivity. Conclusions/Significance: IL-2 mediates the cooperation of memory-like CD4 + and CD8 + T cells in the breakdown of crosstolerance, resulting in effector cytotoxic T lymphocyte differentiation and the induction of autoimmune disease

The Evolution of Primate Short-Term Memory.

Short-term memory is implicated in a range of cognitive abilities and is critical for understanding primate cognitive evolution. To investigate the effects of phylogeny, ecology and sociality on short-term memory, we tested the largest and most diverse primate sample to date (421 non-human primates across 41 species) in an experimental delayed-response task. Our results confirm previous findings that longer delays decrease memory performance across species and taxa. Our analyses demonstrate a considerable contribution of phylogeny over ecological and social factors on the distribution of short-term memory performance in primates; closely related species had more similar short-term memory abilities. Overall, individuals in the branch of Hominoidea performed better compared to Cercopithecoidea, who in turn performed above Platyrrhini and Strepsirrhini. Interdependencies between phylogeny and socioecology of a given species presented an obstacle to disentangling the effects of each of these factors on the evolution of short-term memory capacity. However, this study offers an important step forward in understanding the interspecies and individual variation in short-term memory ability by providing the first phylogenetic reconstruction of this trait’s evolutionary history. The dataset constitutes a unique resource for studying the evolution of primate cognition and the role of short-term memory in other cognitive abilities.info:eu-repo/semantics/publishedVersio

Establishing an infrastructure for collaboration in primate cognition research

Inferring the evolutionary history of cognitive abilities requires large and diverse samples. However, such samples are often beyond the reach of individual researchers or institutions, and studies are often limited to small numbers of species. Consequently, methodological and site-specific-differences across studies can limit comparisons between species. Here we introduce the ManyPrimates project, which addresses these challenges by providing a large-scale collaborative framework for comparative studies in primate cognition. To demonstrate the viability of the project we conducted a case study of short-term memory. In this initial study, we were able to include 176 individuals from 12 primate species housed at 11 sites across Africa, Asia, North America and Europe. All subjects were tested in a delayed-response task using consistent methodology across sites. Individuals could access food rewards by remembering the position of the hidden reward after a 0, 15, or 30-second delay. Overall, individuals performed better with shorter delays, as predicted by previous studies. Phylogenetic analysis revealed a strong phylogenetic signal for short-term memory. Although, with only 12 species, the validity of this analysis is limited, our initial results demonstrate the feasibility of a large, collaborative open-science project. We present the ManyPrimates project as an exciting opportunity to address open questions in primate cognition and behaviour with large, diverse datasets

Establishing an infrastructure for collaboration in primate cognition research

Inferring the evolutionary history of cognitive abilities requires large and diverse samples. However, such samples are often beyond the reach of individual researchers or institutions, and studies are often limited to small numbers of species. Consequently, methodological and site-specific-differences across studies can limit comparisons between species. Here we introduce the ManyPrimates project, which addresses these challenges by providing a large-scale collaborative framework for comparative studies in primate cognition. To demonstrate the viability of the project we conducted a case study of short-term memory. In this initial study, we were able to include 176 individuals from 12 primate species housed at 11 sites across Africa, Asia, North America and Europe. All subjects were tested in a delayed-response task using consistent methodology across sites. Individuals could access food rewards by remembering the position of the hidden reward after a 0, 15, or 30-second delay. Overall, individuals performed better with shorter delays, as predicted by previous studies. Phylogenetic analysis revealed a strong phylogenetic signal for short-term memory. Although, with only 12 species, the validity of this analysis is limited, our initial results demonstrate the feasibility of a large, collaborative open-science project. We present the ManyPrimates project as an exciting opportunity to address open questions in primate cognition and behaviour with large, diverse datasets

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men