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Bacteria encode a complex repertoire of innate immune systems to fend off viruses. Over 150 defense systems disseminated throughout bacterial genomes have now been shown to block viral infection via diverse molecular mechanisms. Multiple components of eukaryotic innate immunity were shown to have bacterial homologs that function in antiviral defense, such as gasdermins, cGAS-STING, and argonautes. These immune pathways likely emerged in bacteria, transmitted to eukaryotes over the course of evolution. New findings on innate immune pathways in one domain of life can provide novel hypotheses in other domains of life. Bacteria might be the source of novel immune proteins across the tree of life. ATP nucleosidases have been reported in diverse prokaryotic and eukaryotic organisms, and homologs of the Eleos and Lamassu bacterial defense systems might be encoded in the human genome. Living cells encode diverse innate immune mechanisms to block pathogens. Bacteria encode a large repertoire of immune strategies, some of which may have been transmitted all the way to humans over the course of evolution. Dissecting the immune mechanisms of bacteria can expand our understanding of innate immunity in all domains of life. Pathogens have fueled the diversification of intracellular defense strategies that collectively define cell-autonomous innate immunity. In bacteria, innate immunity is manifested by a broad arsenal of defense systems that provide protection against bacterial viruses, called phages. The complexity of the bacterial immune repertoire has only been realized recently and is now suggesting that innate immunity has commonalities across the tree of life: many components of eukaryotic innate immunity are found in bacteria where they protect against phages, including the cGAS-STING pathway, gasdermins, and viperins. Here, I summarize recent findings on the conservation of innate immune pathways between prokaryotes and eukaryotes and hypothesize that bacterial defense mechanisms can catalyze the discovery of novel molecular players of eukaryotic innate immunity. [ABSTRACT FROM AUTHOR]

To decarbonize the heating sector, the 4th and 5th generations of district heating networks have been identified as promising solutions. They offer superior energy efficiency, economic viability, and environmental advantages compared to decentralized, individual heating systems. However, they raise several challenges concerning their design and control optimization due to their size and the operational constraints of the production systems involved such as inertial heat generators, intermittent renewable energy sources and thermal energy storage. As a result, numerical simulations of these networks are computationally heavy which makes fast optimal control a complex and challenging task. A common strategy to address this limitation is to formulate reduced order models or to establish fast and yet accurate surrogate models. In this work, we present a novel surrogate modeling framework to rapidly predict district heating networks transients. Our model is based on a physics-guided spatio-temporal convolutional graph neural network. While similar work focused mainly on the prediction of thermal loads, this paper tackles the challenge of simulating complex and non-linear behaviors of the distribution network of district heating systems. The results show that the simulation time using our model is 99% less than a physical simulator while maintaining a high accuracy. In addition, we have conducted an ablation study and a residual analysis to test the robustness of the proposed model. Furthermore, the generalization ability of our approach is assessed by evaluating it against different district heating network topologies. • A spatio-temporal graph neural network is used to predict district heating network dynamics. • A framework enables interaction between physical simulator and surrogate model. • The model achieves high accuracy and captures diverse network dynamics. • Computation time reduction unlocks global optimization with full dynamics of the system. [ABSTRACT FROM AUTHOR]

It is commonly asserted that when extrinsic mortality is high, individuals should invest early in reproduction. This intuition thrives in the literature on life-history theory and human behavior, yet it has been criticized repeatedly on the basis of mathematical models. The intuition is indeed wrong; but a recent theoretical criticism has confused the reason why it is wrong, thereby obscuring earlier and sounder criticisms. In the present article, based on the simplest possible model, we sought to clarify these issues. We confirm earlier findings that extrinsic mortality can affect the evolution of pace of life, not because it leaves little time to reproduce, but through its effects on density-dependent competition. This result highlights the importance of accounting for density-dependence in theoretical models and data analyses. Further, we find little support for the recent claim that the direction of selection on a reaction norm in a variable environment cannot be easily inferred from models made in homogeneous environments. In conclusion, although life-history theory is still imperfect, it has provided simple results that deserve to be understood. [ABSTRACT FROM AUTHOR]

• CRISPR screens enable the investigation of gene function in high-throughput. • CRISPR screens can be performed on bacteria or host cells. • Cas9 and dCas9 are used to mutate genes or inhibit their expression respectively. • Pooled and arrayed screens can access different phenotypes. • New CRISPR technologies such as base-editing have a great potential for screening. Recent advances in genomics have uncovered the tremendous diversity and richness of microbial ecosystems. New functional genomics methods are now needed to probe gene function in high-throughput and provide mechanistic insights. Here, we review how the CRISPR toolbox can be used to inactivate, repress or overexpress genes in a sequence-specific manner and how this offers diverse attractive solutions to identify gene function in high-throughput. Developed both in eukaryotes and prokaryotes, CRISPR screening technologies have already provided meaningful insights in microbiology and host-pathogen interactions. In the era of microbiomes, the versatility and the functional diversity of CRISPR-derived tools has the potential to significantly improve our understanding of microbial communities and their interaction with the host. [ABSTRACT FROM AUTHOR]

Bacteria employ a complex arsenal of immune mechanisms to defend themselves against phages. Recent studies demonstrate that these immune mechanisms frequently involve regulated cell death in response to phage infection. By sacrificing infected cells, this strategy prevents the spread of phages within the surrounding population. In this review, we discuss the principles of regulated cell death in bacterial defense, and show that over 70% of sequenced prokaryotes employ this strategy as part of their defensive arsenals. We highlight the modularity of defense systems involving regulated cell death, explaining how shuffling between phage-sensing and cell-killing protein domains dominates their evolution. Some of these defense systems are the evolutionary ancestors of key components of eukaryotic immunity, highlighting their importance in shaping the evolutionary trajectory of immune systems across the tree of life. • Many antiphage systems trigger regulated death of the infected cell. • Regulated cell death protects the nearby population from the spread of infection. • Over 70% of prokaryotic genomes encode systems that defend via regulated cell death. • Modularity and shuffling of protein domains drive the evolution of these systems. • Eukaryotic immune components evolved from bacterial systems involving cell death. [ABSTRACT FROM AUTHOR]

Background Familial Mediterranean fever (FMF) is an IL-1β–dependent autoinflammatory disease caused by mutations of Mediterranean fever (MEFV) encoding pyrin and characterized by inflammatory attacks induced by physical or psychological stress. Objective We investigated the underlying mechanism that links stress-induced inflammatory attacks with neutrophil activation and release of IL-1β–bearing neutrophil extracellular traps (NETs) in patients with FMF. Methods RNA sequencing was performed in peripheral neutrophils from 3 patients with FMF isolated both during attacks and remission, 8 patients in remission, and 8 healthy subjects. NET formation and proteins were analyzed by using confocal immunofluorescence microscopy, immunoblotting, myeloperoxidase-DNA complex ELISA, and flow cytometry. Samples from patients with Still's disease and bacterial infections were used also. Results The stress-related protein regulated in development and DNA damage responses 1 (REDD1) is significantly overexpressed during FMF attacks. Neutrophils from patients with FMF during remission are resistant to autophagy-mediated NET release, which can be overcome through REDD1 induction. Stress-related mediators (eg, epinephrine) decrease this threshold, leading to autophagy-driven NET release, whereas the synchronous inflammatory environment of FMF attack leads to intracellular production of IL-1β and its release through NETs. REDD1 in autolysosomes colocalizes with pyrin and nucleotide-binding domain, leucine-rich repeat/pyrin domain-containing 3. Mutated pyrin prohibits this colocalization, leading to higher IL-1β levels on NETs. Conclusions This study provides a link between stress and initiation of inflammatory attacks in patients with FMF. REDD1 emerges as a regulator of neutrophil function upstream to pyrin, is involved in NET release and regulation of IL-1β, and might constitute an important piece in the IL-1β–mediated inflammation puzzle. [ABSTRACT FROM AUTHOR]

The debate over the role of stochasticity is central in evolutionary biology, often summarised by whether or not evolution is predictable or repeatable. Here we distinguish three types of stochasticity: stochasticity of mutation and variation, of individual life histories and of environmental change. We then explain when stochasticity matters in evolution, distinguishing four broad situations: stochasticity contributes to maladaptation or limits adaptation; it drives evolution on flat fitness landscapes (evolutionary freedom); it might promote jumps from one fitness peak to another (evolutionary revolutions); and it might shape the selection pressures themselves. We show that stochasticity, by directly steering evolution, has become an essential ingredient of evolutionary theory beyond the classical Wright–Fisher or neutralist–selectionist debates. [Copyright &y& Elsevier]

Crosslinked linear polyethylene/branched polyethylene blends have been studied by thermo-oxidation at different temperatures (between 60 °C and 110 °C), which are either below or above the melting temperature of each polyethylene in the blend. The modifications of the chemical structure of both polyethylenes and the blends were monitored by infrared spectroscopy during thermo-oxidation. The same oxidation products could be identified between the linear polyethylene and the branched polyethylene. Chemical derivatization treatments allowed confirming the thermo-oxidation mechanism of polyethylene and the same oxidation products for both polyethylenes. By using an Arrhenius approach, it has been shown that accelerated ageing above 80 °C is not representative of thermal ageing below this temperature. Moreover, it was shown that there was no influence of the physical state of the polymer during thermal ageing on the observed non-Arrhenius behavior. Thus, extrapolating accelerated ageing tests to lower temperatures by an Arrhenius approach in order to predict the lifetime of the polymer leads to critical errors. • 50/50 blend of polyethylene and branched polyethylene undergo higher oxidation rate than other blends. • There is no influence of the physical state on thermal ageing of PE blends. • Caution must be used when predicting lifetime using a simple Arrhenius approach for polyethylene blends. [ABSTRACT FROM AUTHOR]

The life cycle of the black truffle ( Tuber melanosporum ) includes a mating before sporulation: although the species is hermaphroditic, mating turns out to involve parents with very different features, that mostly behave as male or female only, suggesting that this species undergoes forced dioecism. [ABSTRACT FROM AUTHOR]

Abstract: Population genetic structure and subdivision are key factors affecting the evolution of organisms. In this study, we analysed and compared the population genetic structure of the malaria parasite Plasmodium falciparum and its mosquito vector Anopheles gambiae over space and time in the Nianza Province, near Victoria Lake in Kenya. The parasites were collected from mosquitoes caught in six villages separated by up to 68km in 2002 and 2003. A total of 545 oocysts were dissected from 122 infected mosquitoes and genotyped at seven microsatellite markers. Five hundred and forty-seven mosquitoes, both infected and uninfected, were genotyped at eight microsatellites. For the parasite and the vector, the analysis revealed no (or very little) genetic differentiation among villages. This may be explained by high local population sizes for the parasite and the mosquito. The small level of genetic differentiation observed between populations may explain the speed at which antimalarial drug resistance and insecticide resistance spread into the African continent. [Copyright &y& Elsevier]