[Ecology: The blind spot in pathology research]. / Écologie : l'angle mort de la recherche en ACP.

INTRODUCTION: The 2015 Paris Agreement has been the first restrictive agreement in the fight against climate change. The newer generations of pathologists, who feel more anxiety due to environmental problems than their predecessors, are asked to publish research works while they are harder and harder to and in a context of demographical tensions. We wanted to measure the rise of ecology research in pathology since the Paris Agreement. MATERIAL & METHODS: Over a ten years study period (2013-2022), we have identified via PubMed the number of articles in which forty-three terms taken from the sustainable development vocabulary appeared in ten renowned international pathology journals, selected for their SJR index from ScimagoJr and their impact factor, plus the Annales de pathologie, and compared their means of incidence between the 2013-2015 (m1) and 2016-2022 (m2) periods. The same process has been applied for "artificial intelligence", "deep learning" and "digital pathology". RESULTS: A total of 1336 articles have been identified. Only "digital pathology" (fromm1=8,33 to m2=23,29; p=0,010) and "deep learning" (fromm1=0 to m2=10,14; p=0,034) saw their incidence rise significantly. A significant decrease has been observed with "biological" (fromm1=70,00 to m2=56,86; p=0,020). DISCUSSION-CONCLUSIONS: Pathology reacts to trends but research in ecology has remained in the blind spot since 2015. However there seems to be an awakening as editorials, articles and communications in congress have blossomed the last two years.

A Model for Allosteric Communication in Drug Transport by the AcrAB-TolC Tripartite Efflux Pump.

RND family efflux pumps are complex macromolecular machines involved in multidrug resistance by extruding antibiotics from the cell. While structural studies and molecular dynamics simulations have provided insights into the architecture and conformational states of the pumps, the path followed by conformational changes from the inner membrane protein (IMP) to the periplasmic membrane fusion protein (MFP) and to the outer membrane protein (OMP) in tripartite efflux assemblies is not fully understood. Here, we investigated AcrAB-TolC efflux pump's allostery by comparing resting and transport states using difference distance matrices supplemented with evolutionary couplings data and buried surface area measurements. Our analysis indicated that substrate binding by the IMP triggers quaternary level conformational changes in the MFP, which induce OMP to switch from the closed state to the open state, accompanied by a considerable increase in the interface area between the MFP subunits and between the OMPs and MFPs. This suggests that the pump's transport-ready state is at a more favourable energy level than the resting state, but raises the puzzle of how the pump does not become stably trapped in a transport-intermediate state. We propose a model for pump allostery that includes a downhill energetic transition process from a proposed 'activated' transport state back to the resting pump.