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In most bacteria, cell division depends on the tubulin homolog FtsZ and other proteins, such as SepF, that form a complex termed the divisome. Cell division also depends on FtsZ in many archaea, but other components of the divisome are unknown. Here, we demonstrate that a SepF homolog plays important roles in cell division in Haloferax volcanii , a halophilic archaeon that is known to have two FtsZ homologs with slightly different functions (FtsZ1 and FtsZ2). SepF co-localizes with both FtsZ1 and FtsZ2 at midcell. Attempts to generate a sepF deletion mutant were unsuccessful, suggesting an essential role. Indeed, SepF depletion leads to severe cell division defects and formation of large cells. Overexpression of FtsZ1-GFP or FtsZ2-GFP in SepF-depleted cells results in formation of filamentous cells with a high number of FtsZ1 rings, while the number of FtsZ2 rings is not affected. Pull-down assays support that SepF interacts with FtsZ2 but not with FtsZ1, although SepF appears delocalized in the absence of FtsZ1. Archaeal SepF homologs lack a glycine residue known to be important for polymerization and function in bacteria, and purified H. volcanii SepF forms dimers, suggesting that polymerization might not be important for the function of archaeal SepF. In most bacteria, cell division depends on tubulin homolog FtsZ and other proteins, such as SepF. Cell division in many archaea also depends on FtsZ. Here, Nußbaum et al. show that a SepF homolog plays important roles in cell division in Haloferax volcanii , a halophilic archaeon that has two FtsZ homologs.

Bacterial cell division has been studied for decades but reports on the different archaeal cell division systems are rare. In many archaea, cell division depends on the tubulin homolog FtsZ, but further components of the divisome in these archaea are unknown. The halophilic archaeon Haloferax volcanii encodes two FtsZ homologs with different functions in cell division and a putative SepF homolog. In bacteria, SepF is part of the divisome and is recruited early to the FtsZ ring, where it most likely stimulates FtsZ ring formation. H. volcanii SepF co-localized with FtsZ1 and FtsZ2 at midcell. Overexpression of SepF had no effect on cell morphology, but no sepF deletion mutants could be generated. SepF depletion led to a severe cell division defect, resulting in cells with a strongly increased size. Overexpression of FtsZ1- and FtsZ2-GFP in SepF-depleted cells resulted in filamentous cells with an increasing number of FtsZ1 rings depending on the cell length, whereas FtsZ2 rings were not increased. Pull-down assays with HA-tagged SepF identified an interaction with FtsZ2 but not with FtsZ1. Archaeal SepF homologs lack the conserved glycine residue important for polymerization in bacteria and the H. volcanii SepF was purified as a dimer, suggesting that in contrast to the bacterial SepF homologs, polymerization does not seem to be important for its function. A model is proposed where first the FtsZ1 ring is formed and where SepF recruits FtsZ2 to the FtsZ1 ring, resulting in the formation of the FtsZ2 ring. This study provides important novel insights into cell division in archaea and shows that SepF is an important part of the divisome in FtsZ containing archaea. Competing Interest Statement The authors have declared no competing interest.

Oncogene amplification on extrachromosomal DNA (ecDNA) is a common event, driving aggressive tumor growth, drug resistance and shorter survival. Currently, the impact of nonchromosomal oncogene inheritance—random identity by descent—is poorly understood. Also unclear is the impact of ecDNA on somatic variation and selection. Here integrating theoretical models of random segregation, unbiased image analysis, CRISPR-based ecDNA tagging with live-cell imaging and CRISPR-C, we demonstrate that random ecDNA inheritance results in extensive intratumoral ecDNA copy number heterogeneity and rapid adaptation to metabolic stress and targeted treatment. Observed ecDNAs benefit host cell survival or growth and can change within a single cell cycle. ecDNA inheritance can predict, a priori, some of the aggressive features of ecDNA-containing cancers. These properties are facilitated by the ability of ecDNA to rapidly adapt genomes in a way that is not possible through chromosomal oncogene amplification. These results show how the nonchromosomal random inheritance pattern of ecDNA contributes to poor outcomes for patients with cancer. Random segregation of extrachromosomal DNA contributes to intratumoral heterogeneity and facilitates the rapid adaptation of human tumor cells to anticancer drugs.

Introduction Harnessing positive plant–soil feedbacks via crop rotations is a promising strategy for sustainable agriculture. These feedbacks are often context‐dependent, and how soil heterogeneity explains this variation is unknown. Plants influence soil properties, including microbes, by exuding specialized metabolites. Benzoxazinoids, specialized metabolites released by cereals such as wheat and maize, can alter rhizosphere microbiota and performance of plants subsequently growing in the exposed soils and are thus an excellent model to study agriculturally relevant plant–soil feedbacks. Materials and Methods To understand local variation in soil properties on benzoxazinoid‐mediated plant–soil feedbacks, we conditioned plots with wild‐type maize and benzoxazinoid‐deficient bx1 mutants in a grid pattern across a field, and we then grew winter wheat in the following season. We determined accumulation of benzoxazinoids, root‐associated microbial communities, abiotic soil properties and wheat performance in each plot and then assessed their associations. Results We detected a marked gradient in soil chemistry and microbiota across the field. This gradient resulted in significant differences in benzoxazinoid accumulation, which were explained by differential benzoxazinoid degradation rather than exudation. Benzoxazinoid exudation modulated microbial diversity in root and rhizospheres during maize growth, but not during subsequent wheat growth, while the chemical fingerprint of benzoxazinoids persisted. Averaged across the field, we did not detect feedbacks on wheat performance and defence, apart from a transient decrease in biomass during vegetative growth. Closer analysis, however, revealed significant feedbacks along the chemical and microbial gradient of the field, with effects gradually changing from negative to positive along the gradient. Conclusion Overall, this study revealed that plant–soil feedbacks differ in strength and direction within a field and that this variation can be explained by standing chemical and microbial gradients. Understanding within‐field soil heterogeneity is crucial for the future exploitation of plant–soil feedbacks in sustainable precision agriculture.

Along a food chain, microbiomes occur in each component and often contribute to the functioning or the health of their host or environment. ‘One Health’ emphasizes the connectivity of each component’s health. Chemical stress typically causes dysbiotic microbiomes, but it remains unclear whether chemical stressors consistently affect the microbiomes of food chain components. Here, we challenged food chain components, including water, sediments, soil, plants, and animals, with three chemical stresses consisting of arsenic (toxic trace element), benzoxazinoids (bioactive plant metabolites), and terbuthylazine (herbicide). We analysed 1064 microbiomes to assess their commonalities and differences in their stress responses. We found that chemical stressors overall decreased microbiome diversity in soil, but not in the other microbiomes. In response to stress, all food chain communities strongly shifted in their composition, generally becoming compositionally more similar to each other. In addition, we observed stochastic effects in host-associated communities (plant, animal). Dysbiotic microbiomes were characterized by different sets of bacteria, which responded specifically to the three chemical stressors. Microbial co-occurrence patterns significantly shifted with either decreased (water, sediment, plant, animal) or increased (soil) network sparsity and numbers of keystone taxa following stress treatments. These results suggest major re-distribution of specific taxa in the overall stress- and component-specific responses of microbiomes with the community stability of plant and animal microbiomes being the most affected by chemical stresses. Graphical abstract

Although clinical pharmacy is a discipline that emerged in the 1960s, the question of precisely how pharmacists can play a role in therapeutic optimization remains unanswered. In the field of mental health, psychiatric pharmacists are increasingly involved in medication reconciliation and therapeutic patient education (or psychoeducation) to improve medication management and enhance medication adherence, respectively. However, psychiatric pharmacists must now assume a growing role in team-based models of care and engage in shared expertise in psychopharmacology in order to truly invest in therapeutic optimization of psychotropics. The increased skills in psychopharmacology and expertise in psychotherapeutic drug monitoring can contribute to future strengthening of the partnership between psychiatrists and psychiatric pharmacists. We propose a narrative review of the literature in order to show the relevance of a clinical pharmacist specializing in psychiatry. With this in mind, herein we will address: (i) briefly, the areas considered the basis of the deployment of clinical pharmacy in mental health, with medication reconciliation, therapeutic education of the patient, as well as the growing involvement of clinical pharmacists in the multidisciplinary reflection on pharmacotherapeutic decisions; (ii) in more depth, we present data concerning the use of therapeutic drug monitoring and shared expertise in psychopharmacology between psychiatric pharmacists and psychiatrists. These last two points are currently in full development in France through the deployment of Resource and Expertise Centers in PsychoPharmacology (CREPP in French).

The foundational principles of Darwinian evolution are variation, selection, and identity by descent. Oncogene amplification on extrachromosomal DNA (ecDNA) is a common event, driving aggressive tumour growth, drug resistance, and shorter survival in patients1-4. Currently, the impact of non-chromosomal oncogene inheritance—random identity by descent—is not well understood. Neither is the impact of ecDNA on variation and selection. Here, integrating mathematical modeling, unbiased image analysis, CRISPR-based ecDNA tagging, and live-cell imaging, we identify a set of basic “rules” for how random ecDNA inheritance drives oncogene copy number and distribution, resulting in extensive intratumoural ecDNA copy number heterogeneity and rapid adaptation to metabolic stress and targeted cancer treatment. Observed ecDNAs obligatorily benefit host cell survival or growth and can change within a single cell cycle. In studies ranging from well-curated, patient-derived cancer cell cultures to clinical tumour samples from patients with glioblastoma and neuroblastoma treated with oncogene-targeted drugs, we show how these ecDNA inheritance “rules” can predict, a priori, some of the aggressive features of ecDNA-containing cancers. These properties are entailed by their ability to rapidly change their genomes in a way that is not possible for cancers driven by chromosomal oncogene amplification. These results shed new light on how the non-chromosomal random inheritance pattern of ecDNA underlies poor outcomes for cancer patients.

Harnessing positive plant-soil feedbacks via crop rotations is a promising strategy for sustainable agriculture. Plants can influence soil properties including microbes by exuding specialized metabolites. However, the effects are often context dependent and variable. If and how local soil heterogeneity may explain this variation is unknown. Benzoxazinoids are specialized metabolites that are released in high quantities by cereals such as wheat and maize. Benzoxazinoids can alter rhizosphere microbiota and the performance of plants subsequently growing in the exposed soils and are thus an excellent model to study agriculturally relevant plant-soil feedbacks in the field, and to assess how soil factors affect their outcome. To understand the importance of local variation in soil properties on benzoxazinoid-mediated plant-soil feedbacks, we conditioned plots with wild-type maize and benzoxazinoid-deficient bx1 mutant plants in a grid pattern across an arable field. We then grew winter wheat across the entire field in the following season. We determined accumulation of benzoxazinoids, root-associated microbial communities, abiotic soil properties and wheat performance in each plot. We also determined benzoxazinoid conversion dynamics in a labelling experiment under controlled conditions, and then assessed associations between soil chemical variation and benzoxazinoid-mediated plant-soil feedbacks. Across the field, we detected a marked gradient in soil chemical and microbial community composition. This gradient resulted in significant differences in benzoxazinoid accumulation. These differences were explained by differential benzoxazinoid degradation rather than exudation. Benzoxazinoid exudation modulated alpha diversity of root and rhizosphere bacteria and fungi during maize growth, but not during subsequent wheat growth, while the chemical fingerprint of benzoxazinoid accumulation persisted. Averaged across the field, we detected no significant feedback effects of benzoxazinoid conditioning on wheat performance and defence, apart from a transient decrease in biomass during vegetative growth. Closer analysis however, revealed pronounced feedback effects along the chemical and microbial gradient of the field, with effects gradually changing from negative to positive along the gradient. Overall, this study revealed that plant-soil feedbacks differ in strength and direction within a field, and that this variation can be explained by standing chemical and microbial gradients, which strongly affect benzoxazinoid accumulation in the soil. Understanding within-field soil heterogeneity is crucial for the future exploitation of plant-soil feedbacks in sustainable precision agriculture.

Along a food chain, microbiomes occur in each component and often contribute to the functioning or the health of their host or environment. ‘One Health’ emphasizes the connectivity of each component’s health. Chemical stress typically causes dysbiotic microbiomes, but it remains unclear whether chemical stressors consistently affect the microbiomes along food chain components. Here, we systematically challenged a model food chain, including water, sediments, soil, plants, and animals, with three chemical stresses consisting of arsenic (a toxic trace element), benzoxazinoids (an abundant bioactive plant metabolites), and terbuthylazine (an herbicide typically found along a human food chain). The analysis of 1,064 microbiome profiles for commonalities and differences in their stress responses indicated that chemical stressors decreased microbiome diversity in soil and animal, but not in the other microbiomes. In response to stress, all food chain communities strongly shifted in their composition, generally becoming compositionally more similar to each other. In addition, we observed stochastic effects in host-associated communities (plant, animal). Dysbiotic microbiomes were characterized by different sets of bacteria, which responded specifically to the three chemical stressors. Microbial co-occurrence patterns significantly shifted with either decreased (water, sediment, plant, animal) or increased (soil) network sparsity and numbers of keystone taxa following stress treatments. This suggested major re-distribution of the roles that specific taxa may have, with the community stability of plant and animal microbiomes being the most affected by chemical stresses. Overall, we observed stress- and component-specific responses to chemical stressors in microbiomes along the model food chain, which could have implications on food chain health.