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In mammals, interactions between sequences within topologically associating domains enable control of gene expression across large genomic distances. Yet it is unknown how frequently such contacts occur, how long they last and how they depend on the dynamics of chromosome folding and loop extrusion activity of cohesin. By imaging chromosomal locations at high spatial and temporal resolution in living cells, we show that interactions within topologically associating domains are transient and occur frequently during the course of a cell cycle. Interactions become more frequent and longer in the presence of convergent CTCF sites, resulting in suppression of variability in chromosome folding across time. Supported by physical models of chromosome dynamics, our data suggest that CTCF-anchored loops last around 10 min. Our results show that long-range transcriptional regulation might rely on transient physical proximity, and that cohesin and CTCF stabilize highly dynamic chromosome structures, facilitating selected subsets of chromosomal interactions. Live-cell imaging shows that interactions within topologically associating domains are transient and frequent throughout the cell cycle. Convergent CTCF sites regulate the frequency and duration of interactions, which last a few minutes on average.

Optic atrophy 1 (OPA1) is a mitochondrial inner membrane protein that has an important role in mitochondrial fusion and structural integrity. Dysfunctional OPA1 mutations cause atrophy of the optic nerve leading to blindness. Here, we show that OPA1 has an important role in the innate immune system. Using conditional knockout mice lacking Opa1 in neutrophils ( Opa1 N∆ ), we report that lack of OPA1 reduces the activity of mitochondrial electron transport complex I in neutrophils. This then causes a decline in adenosine-triphosphate (ATP) production through glycolysis due to lowered NAD + availability. Additionally, we show that OPA1-dependent ATP production in these cells is required for microtubule network assembly and for the formation of neutrophil extracellular traps. Finally, we show that Opa1 N∆ mice exhibit a reduced antibacterial defense capability against Pseudomonas aeruginosa . Optic atrophy 1 (OPA1) is known to be important for mitochondrial fusion and structural integrity. Here, using OPA1 knockout mice, the authors show a detrimental effect on host defense capabilities against pathogen infections. This study reports a critical role for OPA1 in innate immunity.

The community-driven initiative Quality Assessment and Reproducibility for Instruments & Images in Light Microscopy (QUAREP-LiMi) wants to improve reproducibility for light microscopy image data through quality control (QC) management of instruments and images. It aims for a common set of QC guidelines for hardware calibration and image acquisition, management and analysis.

The ability of a retinoid X receptor (RXR) to heterodimerize with many nuclear receptors, including LXR, PPAR, NGF1B and RAR, underscores its pivotal role within the nuclear receptor superfamily. Among these heterodimers, PPAR:RXR is considered an important signalling mediator of both PPAR ligands, such as fatty acids, and 9‐ cis retinoic acid (9‐ cis RA), an RXR ligand. In contrast, the existence of an RXR/9‐ cis RA signalling pathway independent of PPAR or any other dimerization partner remains disputed. Using in vivo chromatin immunoprecipitation, we now show that RXR homodimers can selectively bind to functional PPREs and induce transactivation. At the molecular level, this pathway requires stabilization of the homodimer–DNA complexes through ligand‐dependent interaction with the coactivator SRC1 or TIF2. This pathway operates both in the absence and in the presence of PPAR, as assessed in cells carrying inactivating mutations in PPAR genes and in wild‐type cells. In addition, this signalling pathway via PPREs is fully functional and can rescue the severe hypothermia phenotype observed in fasted PPARα −/− mice. These observations have important pharmacological implications for the development of new rexinoid‐based treatments.

Images document scientific discoveries and are prevalent in modern biomedical research. Microscopy imaging in particular is currently undergoing rapid technological advancements. However, for scientists wishing to publish obtained images and image-analysis results, there are currently no unified guidelines for best practices. Consequently, microscopy images and image data in publications may be unclear or difficult to interpret. Here, we present community-developed checklists for preparing light microscopy images and describing image analyses for publications. These checklists offer authors, readers and publishers key recommendations for image formatting and annotation, color selection, data availability and reporting image-analysis workflows. The goal of our guidelines is to increase the clarity and reproducibility of image figures and thereby to heighten the quality and explanatory power of microscopy data. Community-developed checklists offer best-practice guidance for biologists preparing light microscopy images and describing image analyses for publications.

Background: The modulation of energetic homeostasis by pollutants has recently emerged as a potential contributor to the onset of metabolic disorders. Diethylhexyl phthalate (DEHP) is a widely used industrial plasticizer to which humans are widely exposed. Phthalates can activate the three peroxisome proliferator—activated receptor (PPAR) isotypes on cellular models and induce peroxisome proliferation in rodents. Objectives: In this study, we aimed to evaluate the systemic and metabolic consequences of DEHP exposure that have remained so far unexplored and to characterize the underlying molecular mechanisms of action. Methods: As a proof of concept and mechanism, genetically engineered mouse models of PPARs were exposed to high doses of DEHP, followed by metabolic and molecular analyses. Results: DEHP-treated mice were protected from diet-induced obesity via PPARα-dependent activation of hepatic fatty acid catabolism, whereas the activity of neither PPARβ nor PPARγ was affected. However, the lean phenotype observed in response to DEHP in wild-type mice was surprisingly abolished in PPARα-humanized mice. These species differences are associated with a different pattern of coregulator recruitment. Conclusion: These results demonstrate that DEHP exerts species-specific metabolic actions that rely to a large extent on PPARα signaling and highlight the metabolic importance of the species-specific activation of PPARα by xenobiotic compounds.

The modulation of energetic homeostasis by pollutants has recently emerged as a potential contributor to the onset of metabolic disorders. Diethylhexyl phthalate (DEHP) is a widely used industrial plasticizer to which humans are widely exposed. Phthalates can activate the three peroxisome proliferator-activated receptor (PPAR) isotypes on cellular models and induce peroxisome proliferation in rodents. In this study, we aimed to evaluate the systemic and metabolic consequences of DEHP exposure that have remained so far unexplored and to characterize the underlying molecular mechanisms of action. As a proof of concept and mechanism, genetically engineered mouse models of PPARs were exposed to high doses of DEHP, followed by metabolic and molecular analyses. DEHP-treated mice were protected from diet-induced obesity via PPARalpha-dependent activation of hepatic fatty acid catabolism, whereas the activity of neither PPARbeta nor PPARgamma was affected. However, the lean phenotype observed in response to DEHP in wild-type mice was surprisingly abolished in PPARalpha-humanized mice. These species differences are associated with a different pattern of coregulator recruitment. These results demonstrate that DEHP exerts species-specific metabolic actions that rely to a large extent on PPARalpha signaling and highlight the metabolic importance of the species-specific activation of PPARalpha by xenobiotic compounds.

The performance of a confocal imaging system may be no better than a general-purpose widefield system if it is not properly maintained or quality controlled. The publication of ISO 21073, 'Confocal microscopes- Optical data of fluorescence confocal microscopes for biological imaging', set a standard for the minimal Quality Control (QC) that should be performed for Confocal Microscopes. Here we describe methodology for performing the QC requirements to satisfy ISO 21073, as well as suggesting other QC methods that should be performed to obtain a minimum level of information about the microscope system.