Feedback from supermassive black holes transforms centrals into passive galaxies by ejecting circumgalactic gas

Davies et al. (2019) established that for L^* galaxies the fraction of baryons in the circumgalactic medium (CGM) is inversely correlated with the mass of their central supermassive black holes (BHs) in the EAGLE hydrodynamic simulation. The interpretation is that, over time, a more massive BH has provided more energy to transport baryons beyond the virial radius, which additionally reduces gas accretion and star formation. We continue this research by focusing on the relationship between the 1) BH masses, 2) physical and observational properties of the CGM, and 3) galaxy colours for Milky Way-mass systems. The ratio of the cumulative BH feedback energy over the gaseous halo binding energy is a strong predictor of the CGM gas content, with BHs injecting >~10x the binding energy resulting in gas-poor haloes. Observable tracers of the CGM, including CIV, OVI, and HI absorption line measurements, are found to be effective tracers of the total z~0 CGM halo mass. We use high-cadence simulation outputs to demonstrate that BH feedback pushes baryons beyond the virial radius within 100 Myr timescales, but that CGM metal tracers take longer (0.5-2.5 Gyr) to respond. Secular evolution of galaxies results in blue, star-forming or red, passive populations depending on the cumulative feedback from BHs. The reddest quartile of galaxies with M_*=10^{10.2-10.7} M_solar (median u-r = 2.28) has a CGM mass that is 2.5x lower than the bluest quartile (u-r=1.59). We propose strategies for observing the predicted lower CGM column densities and covering fractions around galaxies hosting more massive BHs using the Cosmic Origins Spectrograph on Hubble

The role of ubiquitination and hepatocyte growth factor-regulated tyrosine kinase substrate in the degradation of the adrenomedullin type I receptor

Calcitonin receptor-like receptor (CLR) and the receptor activity-modifying protein 2 (RAMP2) comprise a receptor for adrenomedullin (AM). Although it is known that AM induces internalization of CLR•RAMP2, little is known about the molecular mechanisms that regulate the trafficking of CLR•RAMP2. Using HEK and HMEC-1 cells, we observed that AM-induced activation of CLR•RAMP2 promoted ubiquitination of CLR. A mutant (CLRΔ9KR), lacking all intracellular lysine residues was functional and trafficked similar to the wild-type receptor, but was not ubiquitinated. Degradation of CLR•RAMP2 and CLRΔ9KR•RAMP2 was not dependent on the duration of AM stimulation or ubiquitination and occurred via a mechanism that was partially prevented by peptidase inhibitors. Degradation of CLR•RAMP2 was sensitive to overexpression of hepatocyte growth factor-regulated tyrosine kinase substrate (HRS), but not to HRS knockdown, whereas CLRΔ9KR•RAMP2 degradation was unaffected. Overexpression, but not knockdown of HRS, promoted hyperubiquitination of CLR under basal conditions. Thus, we propose a role for ubiquitin and HRS in the regulation of AM-induced degradation of CLR•RAMP2

Quasar Sightline and Galaxy Evolution (QSAGE) - III. The mass-metallicity and fundamental metallicity relation of z ≈ 2.2 galaxies

We present analysis of the mass-metallicity relation (MZR) for a sample of 67 [O iii]-selected star-forming (SF) galaxies at a redshift range of z = 1.99-2.32 (zmed = 2.16) using Hubble Space Telescope Wide Field Camera 3 grism spectroscopy from the Quasar Sightline and Galaxy Evolution survey. Metallicities were determined using empirical gas-phase metallicity calibrations based on the strong emission lines [O ii]3727, 3729, [O iii]4959, 5007 and Hβ. SF galaxies were identified, and distinguished from active-galactic nuclei, via Mass-Excitation diagrams. Using z ∼0 metallicity calibrations, we observe a negative offset in the z = 2.2 MZR of ≈-0.51 dex in metallicity when compared to locally derived relationships, in agreement with previous literature analysis. A similar offset of ≈-0.46 dex in metallicity is found when using empirical metallicity calibrations that are suitable out to z ∼5, though our z = 2.2 MZR, in this case, has a shallower slope. We find agreement between our MZR and those predicted from various galaxy evolution models and simulations. Additionally, we explore the extended fundamental metallicity relation (FMR) which includes an additional dependence on star formation rate. Our results consistently support the existence of the FMR, as well as revealing an offset of 0.28 ± 0.04 dex in metallicity compared to locally derived relationships, consistent with previous studies at similar redshifts. We interpret the negative correlation with SFR at fixed mass, inferred from an FMR existing for our sample, as being caused by the efficient accretion of metal-poor gas fuelling SFR at cosmic noon

Integrating ecology and evolutionary theory. A game changer for biodiversity conservation?

Currently, one of the central arguments in favour of biodiversity conservation is that it is essential for the maintenance of ecosystem services, that is, the benefits that people receive from ecosystems. However, the relationship between ecosystem services and biodiversity is contested and needs clarification. The goal of this chapter is to spell out the interaction and reciprocal influences between conservation science, evolutionary biology, and ecology, in order to understand whether a stronger integration of evolutionary and ecological studies might help clarify the interaction between biodiversity and ecosystem functioning as well as influence biodiversity conservation practices. To this end, the eco-evolutionary feedback theory proposed by David Post and Eric Palkovacs is analysed, arguing that it helps operationalise niche construction theory and develop a more sophisticated understanding of the relationship between ecosystem functioning and biodiversity. Finally, it is proposed that by deepening the integration of ecological and evolutionary factors in our understanding of ecosystem functioning, the eco-evolutionary feedback theory is supportive of an “evolutionary-enlightened management” of biodiversity within the ecosystem services approach.info:eu-repo/semantics/publishedVersio

Integrated genomic characterization of oesophageal carcinoma

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies.ope

Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

Summary Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (TP53, ATRX, RB1) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types

Comprehensive molecular characterization of the hippo signaling pathway in cancer

Hippo signaling has been recognized as a key tumor suppressor pathway. Here, we perform a comprehensive molecular characterization of 19 Hippo core genes in 9,125 tumor samples across 33 cancer types using multidimensional “omic” data from The Cancer Genome Atlas. We identify somatic drivers among Hippo genes and the related microRNA (miRNA) regulators, and using functional genomic approaches, we experimentally characterize YAP and TAZ mutation effects and miR-590 and miR-200a regulation for TAZ. Hippo pathway activity is best characterized by a YAP/TAZ transcriptional target signature of 22 genes, which shows robust prognostic power across cancer types. Our elastic-net integrated modeling further reveals cancer-type-specific pathway regulators and associated cancer drivers. Our results highlight the importance of Hippo signaling in squamous cell cancers, characterized by frequent amplification of YAP/TAZ, high expression heterogeneity, and significant prognostic patterns. This study represents a systems-biology approach to characterizing key cancer signaling pathways in the post-genomic era

Assessment of damage from implantation of microdialysis probes in the rat hippocampus with silver degeneration staining

We used a sensitive silver degeneration staining method to study the effects of insertion of microdialysis probes in rat dorsal hippocampus and neocortex. Nine animals were sacrificed 24 h, 3 days or 7 days after implantation of dialysis tubing. Although mild neuronal cell death and small petechial hemorrhages were seen in elose proximity to the implantation site, the striking finding was the presence of degenerating axons both adjacent to the implantation site and in remote sites such as the corpus callosum and contralateral hippocampus. The observed changes could alter brain function near or remote from the implantation site and should be considered in analysis of dialysis experiments