When COVID-19 pandemic spread in Europe, governments imposed unprecedented confinement measures with mostly unknown repercussions on contemporary societies. In some cases, a considerable drop in energy consumption was observed, anticipating a scenario of sizable low-cost energy generation, from renewable sources, expected only for years later. In this paper, the impact of governmental restrictions on electrical load, generation and transmission was investigated in 16 European countries. Using the indices provided by the Oxford COVID-19 Government Response Tracker, precise restriction types were found to correlate with the load drop. Then the European grid was analysed to assess how the load drop was balanced by the change in generation and transmission patterns. The same restriction period from 2020 was compared to previous years, accounting for yearly variability with ad hoc statistical technique. As a result, generation was found to be heavily impacted in most countries with significant load drop. Overall, generation from nuclear, and fossil coal and gas sources was reduced, in favour of renewables and, in some countries, fossil gas. Moreover, intermittent renewables generation increased in most countries without indicating an exceptional amount of curtailments. Finally, the European grid helped balance those changes with an increase in both energy exports and imports, with some net exporting countries becoming net importers, notably Germany, and vice versa. Together, these findings show the far reaching implications of the COVID-19 crisis, and contribute to the understanding and planning of higher renewables share scenarios, which will become more prevalent in the battle against climate change.

In the presence of antigen and costimulation, T cells undergo a characteristic response of expansion, cessation and contraction. Previous studies have revealed that population-level reproducibility is a consequence of multiple clones exhibiting considerable disparity in burst size, highlighting the requirement for single-cell information in understanding T-cell fate regulation. Here we show that individual T-cell clones resulting from controlled stimulation in vitro are strongly lineage imprinted with highly correlated expansion fates. Progeny from clonal families cease dividing in the same or adjacent generations, with inter-clonal variation producing burst-size diversity. The effects of costimulatory signals on individual clones sum together with stochastic independence; therefore, the net effect across multiple clones produces consistent, but heterogeneous population responses. These data demonstrate that substantial clonal heterogeneity arises through differences in experience of clonal progenitors, either through stochastic antigen interaction or by differences in initial receptor sensitivities.

Lymphocytes are the central actors in adaptive immune responses. When challenged with antigen, a small number of B and T cells have a cognate receptor capable of recognising and responding to the insult. These cells proliferate, building an exponentially growing, differentiating clone army to fight off the threat, before ceasing to divide and dying over a period of weeks, leaving in their wake memory cells that are primed to rapidly respond to any repeated infection. Due to the non-linearity of lymphocyte population dynamics, mathematical models are needed to interrogate data from experimental studies. Due to lack of evidence to the contrary and appealing to arguments based on Occam’s Razor, in these models newly born progeny are typically assumed to behave independently of their predecessors. Recent experimental studies, however, challenge that assumption, making clear that there is substantial inheritance of timed fate changes from each cell by its offspring, calling for a revision to the existing mathematical modelling paradigms used for information extraction. By assessing long-term live-cell imaging of stimulated murine B and T cells in vitro, we distilled the key phenomena of these within-family inheritances and used them to develop a new mathematical model, Cyton2, that encapsulates them. We establish the model’s consistency with these newly observed fine-grained features. Two natural concerns for any model that includes familial correlations would be that it is overparameterised or computationally inefficient in data fitting, but neither is the case for Cyton2. We demonstrate Cyton2’s utility by challenging it with high-throughput flow cytometry data, which confirms the robustness of its parameter estimation as well as its ability to extract biological meaning from complex mixed stimulation experiments. Cyton2, therefore, offers an alternate mathematical model, one that is, more aligned to experimental observation, for drawing inferences on lymphocyte population dynamics.

The generation of cellular heterogeneity is an essential feature of immune responses. Understanding the heritability and asymmetry of phenotypic changes throughout this process requires determination of clonal-level contributions to fate selection. Evaluating intraclonal and interclonal heterogeneity and the influence of distinct fate determinants in large numbers of cell lineages, however, is usually laborious, requiring familial tracing and fate mapping. In this study, we introduce a novel, accessible, high-throughput method for measuring familial fate changes with accompanying statistical tools for testing hypotheses. The method combines multiplexing of division tracking dyes with detection of phenotypic markers to reveal clonal lineage properties. We illustrate the method by studying in vitro-activated mouse CD8 T cell cultures, reporting division and phenotypic changes at the level of families. This approach has broad utility as it is flexible and adaptable to many cell types and to modifications of in vitro, and potentially in vivo, fate monitoring systems.

High-throughput single cell methods have uncovered substantial heterogeneity in the pool of hematopoietic stem and progenitor cells (HSPCs), but how much instruction is inherited by offspring from their heterogeneous ancestors remains unanswered. Using a method that enables simultaneous determination of common ancestor, division number, and differentiation status of a large collection of single cells, our data revealed that murine cells that derived from a common ancestor had significant similarities in their division progression and differentiation outcomes. Although each family diversifies, the overall collection of cell types observed is composed of homogeneous families. Heterogeneity between families could be explained, in part, by differences in ancestral expression of cell-surface markers. Our analyses demonstrate that fate decision by cells are largely inherited from ancestor cells, indicating the importance of common ancestor effects. These results may have ramifications for bone marrow transplantation and leukemia, where substantial heterogeneity in HSPC behavior is observed.

The advent of high throughput single cell methods such as scRNA-seq has uncovered substantial heterogeneity in the pool of hematopoietic stem and progenitor cells (HSPCs). A significant issue is how to reconcile those findings with the standard model of hematopoietic development, and a fundamental question is how much instruction is inherited by offspring from their ancestors. To address this, we further developed a high-throughput method that enables simultaneously determination of common ancestor, generation, and differentiation status of a large collection of single cells. Data from it revealed that while there is substantial population-level heterogeneity, cells that derived from a common ancestor were highly concordant in their division progression and share similar differentiation outcomes, revealing significant familial effects on both division and differentiation. Although each family diversifies to some extent, the overall collection of cell types observed in a population is largely composed of homogeneous families from heterogeneous ancestors. Heterogeneity between families could be explained, in part, by differences in ancestral expression of cellsurface markers that are used for phenotypic HSPC identification: CD48, SCA-1, c-kit and Flt3. These data call for a revision of the fundamental model of haematopoiesis from a single tree to an ensemble of trees from distinct ancestors where common ancestor effect must be considered. As HSPCs are cultured in the clinic before bone marrow transplantation, our results suggest that the broad range of engraftment and proliferation capacities of HSPCs could be consequences of the heterogeneity in their engrafted families, and altered culture conditions might reduce heterogeneity between families, possibly improving transplantation outcomes.

Social dialogue, the foundation of our democracies, is currently threatened by disinformation and partisanship, with their disrupting role on individual and collective awareness and detrimental effects on decisionmaking processes. Despite a great deal of attention to the news sphere itself, little is known about the subtle interplay between the offer and the demand for information. Still, a broader perspective on the news ecosystem, including both the producers and the consumers of information, is needed to build new tools to assess the health of the infosphere. Here, we combine in the same framework news supply, as mirrored by a fairly complete Italian news database -partially annotated for fake news, and news demand, as captured through the Google Trends data for Italy. Our investigation focuses on the temporal and semantic interplay of news, fake news, and searches in several domains, including the virus SARS-CoV-2 pandemic. Two main results emerge. First, disinformation is extremely reactive to people's interests and tends to thrive, especially when there is a mismatch between what people are interested in and what news outlets provide. Second, a suitably defined index can assess the level of disinformation only based on the available volumes of news and searches. Although our results mainly concern the Coronavirus subject, we provide hints that the same findings can have more general applications. We contend these results can be a powerful asset in informing campaigns against disinformation and providing news outlets and institutions with potentially relevant strategies.

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