The Helicobacter pylori Heat-Shock Repressor HspR: Definition of Its Direct Regulon and Characterization of the Cooperative DNA-Binding Mechanism on Its Own Promoter

The ability of pathogens to perceive environmental conditions and modulate gene expression accordingly is a crucial feature for bacterial survival. In this respect, the heat-shock response, a universal cellular response, allows cells to adapt to hostile environmental conditions and to survive during stress. In the major human pathogen Helicobacter pylori the expression of chaperone-encoding operons is under control of two auto-regulated transcriptional repressors, HrcA and HspR, with the latter acting as the master regulator of the regulatory circuit. To further characterize the HspR regulon in H. pylori, we used global transcriptome analysis (RNA-sequencing) in combination with Chromatin Immunoprecipitation coupled with deep sequencing (ChIP-sequencing) of HspR genomic binding sites. Intriguingly, these analyses showed that HspR is involved in the regulation of different crucial cellular functions through a limited number of genomic binding sites. Moreover, we further characterized HspR-DNA interactions through hydroxyl-radical footprinting assays. This analysis in combination with a nucleotide sequence alignment of HspR binding sites, revealed a peculiar pattern of DNA protection and highlighted sequence conservation with the HAIR motif (an HspR-associated inverted repeat of Streptomyces spp.). Site-directed mutagenesis demonstrated that the HAIR motif is fundamental for HspR binding and that additional nucleotide determinants flanking the HAIR motif are required for complete binding of HspR to its operator sequence spanning over 70 bp of DNA. This finding is compatible with a model in which possibly a dimer of HspR recognizes the HAIR motif overlapping its promoter for binding and in turn cooperatively recruits two additional dimers on both sides of the HAIR motif

Global mean climate and main patterns of variability in the CMCC-CM2 coupled model

Euro‐Mediterranean Centre on Climate Change coupled climate model (CMCC‐CM2) represents the new family of the global coupled climate models developed and used at CMCC. It is based on the atmospheric, land and sea ice components from the Community Earth System Model coupled with the global ocean model Nucleus for European Modeling of the Ocean. This study documents the model components, the coupling strategy, particularly for the oceanic, atmospheric, and sea ice components, and the overall model ability in reproducing the observed mean climate and main patterns of interannual variability. As a first step toward a more comprehensive, process‐oriented, validation of the model, this work analyzes a 200‐year simulation performed under constant forcing corresponding to present‐day climate conditions. In terms of mean climate, the model is able to realistically reproduce the main patterns of temperature, precipitation, and winds. Specifically, we report improvements in the representation of the sea surface temperature with respect to the previous version of the model. In terms of mean atmospheric circulation features, we notice a realistic simulation of upper tropospheric winds and midtroposphere geopotential eddies. The oceanic heat transport and the Atlantic meridional overturning circulation satisfactorily compare with present‐day observations and estimates from global ocean reanalyses. The sea ice patterns and associated seasonal variations are realistically reproduced in both hemispheres, with a better skill in winter. Main weaknesses of the simulated climate are related with the precipitation patterns, specifically in the tropical regions with large dry biases over the Amazon basin. Similarly, the seasonal precipitation associated with the monsoons, mostly over Asia, is weaker than observed. The main patterns of interannual variability in terms of dominant empirical orthogonal functions are faithfully reproduced, mostly in the Northern Hemisphere winter. In the tropics the main teleconnection patterns associated with El Niño–Southern Oscillation and with the Indian Ocean Dipole are also in good agreement with observations.Published4A. Oceanografia e climaJCR Journa

Radiomics and artificial intelligence in prostate cancer: new tools for molecular hybrid imaging and theragnostics

In prostate cancer (PCa), the use of new radiopharmaceuticals has improved the accuracy of diagnosis and staging, refined surveillance strategies, and introduced specific and personalized radioreceptor therapies. Nuclear medicine, therefore, holds great promise for improving the quality of life of PCa patients, through managing and processing a vast amount of molecular imaging data and beyond, using a multi-omics approach and improving patients' risk-stratification for tailored medicine. Artificial intelligence (AI) and radiomics may allow clinicians to improve the overall efficiency and accuracy of using these "big data" in both the diagnostic and theragnostic field: from technical aspects (such as semi-automatization of tumor segmentation, image reconstruction, and interpretation) to clinical outcomes, improving a deeper understanding of the molecular environment of PCa, refining personalized treatment strategies, and increasing the ability to predict the outcome. This systematic review aims to describe the current literature on AI and radiomics applied to molecular imaging of prostate cancer

Ice flux evolution in fast flowing areas of the Greenland ice sheet over the 20th and 21st centuries

International audienceThis study investigates the evolution of Greenland ice sheet flux focusing on five of the main fast flowing regions (Petermann glacier, North East Greenland Ice Stream, Kangerdlugssuaq glacier, Helheim glacier and Jakobshavn glacier) in response to 20th and 21st century climate change. A hybrid (shallow ice and shallow shelf) ice-sheet model (ISM) is forced with the combined outputs of a set of seven CMIP5 models and the regional climate model MAR. The ISM simulates the present-day ice velocity pattern, topography and surface mass balance (SMB) in good agreement with observations. Except for the Kangerdlugssuaq glacier, over the 21st century all the fast-flowing areas have exhibited a decrease in ice flux as a result of a negative SMB rather than dynamical changes. Only the fronts of Kangerdlugssuaq and Helheim glaciers have shown an interannual variability driven by dynamical rather than climate changes. Finally, the results predict a substantial inland ice margin retreat by the end of the 21st century, especially along the northern coasts

Radiomics and artificial intelligence in prostate cancer: new tools for molecular hybrid imaging and theragnostics

In prostate cancer (PCa), the use of new radiopharmaceuticals has improved the accuracy of diagnosis and staging, refined surveillance strategies, and introduced specific and personalized radioreceptor therapies. Nuclear medicine, therefore, holds great promise for improving the quality of life of PCa patients, through managing and processing a vast amount of molecular imaging data and beyond, using a multi-omics approach and improving patients' risk-stratification for tailored medicine. Artificial intelligence (AI) and radiomics may allow clinicians to improve the overall efficiency and accuracy of using these "big data" in both the diagnostic and theragnostic field: from technical aspects (such as semi-automatization of tumor segmentation, image reconstruction, and interpretation) to clinical outcomes, improving a deeper understanding of the molecular environment of PCa, refining personalized treatment strategies, and increasing the ability to predict the outcome. This systematic review aims to describe the current literature on AI and radiomics applied to molecular imaging of prostate cancer

Prenatal interleukin 6 elevation increases glutamatergic synapse density and disrupts hippocampal connectivity in offspring

Early prenatal inflammatory conditions are thought to be a risk factor for different neurodevelopmental disorders. Maternal interleukin-6 (IL-6) elevation during pregnancy causes abnormal behavior in offspring, but whether these defects result from altered synaptic developmental trajectories remains unclear. Here we showed that transient IL-6 elevation via injection into pregnant mice or developing embryos enhanced glutamatergic synapses and led to overall brain hyperconnectivity in offspring into adulthood. IL-6 activated synaptogenesis gene programs in glutamatergic neurons and required the transcription factor STAT3 and expression of the RGS4 gene. The STAT3-RGS4 pathway was also activated in neonatal brains during poly(I:C)-induced maternal immune activation, which mimics viral infection during pregnancy. These findings indicate that IL-6 elevation at early developmental stages is sufficient to exert a long-lasting effect on glutamatergic synaptogenesis and brain connectivity, providing a mechanistic framework for the association between prenatal inflammatory events and brain neurodevelopmental disorders