Notes

Dihydrotanshinone I Particularly Suppresses NLRP3 Inflammasome Service and also Protects Against Septic Distress Throughout Vivo.
Having long-term familiar neighbors - rather than kin neighbors - can increase survival and double reproductive success in North American red squirrels. These benefits are so high they can slow senescence and may explain numerous social behaviors in this otherwise individualistic species.New research reveals a complex interaction between attention and learning across the lifespan. In young adults, attention guides learning. In older adults, attention declines lead to less selective learning. Counterintuitively, however, in children better attention relates to less selective learning.The ability of fungi to immobilize metals is an extraordinary phenomenon. Now, a protein involved in the formation of copper carbonate nanoparticles has been identified, and suggests that the process is under the control of the fungus, opening new avenues for the synthesis of nanomaterials.The discoveries of the photopigment melanopsin and intrinsically photosensitive retinal ganglion cells (ipRGCs) have revealed novel mechanisms of light detection now known to control several kinds of non-image-forming vision, including regulation of mood, the circadian rhythm, and the pupillary light reflex (PLR). These remarkable discoveries have been made mostly on mammals, but many vertebrates express melanopsin and adjust the diameter of the pupil to the ambient light intensity to extend the operating range of vision and reduce spherical aberration1. We were curious to know whether a PLR controlled by melanopsin is also present in lamprey, which are members of the only remaining group of jawless vertebrates (agnathans) which diverged from all other vertebrates about 500 million years ago2. We now show that lamprey have a robust PLR mediated by melanopsin apparently without any contribution from signals of rods and cones, suggesting that non-image-forming perception emerged long before the radiation of present vertebrate lines and was already present in the late Cambrian.The effort to reconstruct the tree of life was revolutionized by the use of sequences of proteins and nucleic acids. Phylogenetic trees are now routinely inferred using hundreds of thousands of amino acid or nucleotide characters. It thus seems surprising that many aspects of the tree of life are still controversial; conflicting results between large scale phylogenomic studies show that errors remain common despite large datasets. These errors often result from systematic biases in the way sequences evolve. While the resulting systematic errors are well understood, it requires careful efforts to reduce their effects.Jessica Ware introduces the insect order odonatan, the damselflies and dragon flies.Interview with Josh Dubnau, who studies the role of mobile retrotransposable elements on both normal brain aging and age-related neurodegenerative diseases at Stony Brook University.Recent functional and proteomic studies in eukaryotes (www.openprot.org) predict the translation of alternative open reading frames (AltORFs) in mature G protein-coupled receptor (GPCR) mRNAs, including that of bradykinin B2 receptor (B2R). Our main objective was to determine the implication of a newly discovered AltORF resulting-protein, termed AltB2R, in the known signaling properties of B2R using complementary methodological approaches. When ectopically expressed in HeLa cells, AltB2R presented predominant punctate cytoplasmic/perinuclear distribution and apparent co-interaction with B2R at plasma and endosomal/vesicular membranes. PFTα concentration The presence of AltB2R increases intracellular [Ca2+] and ERK1/2-MAPK activation (via phosphorylation) following B2R stimulation. Moreover, HEK293A cells expressing mutant B2R lacking concomitant expression of AltB2R displayed significantly decreased maximal responses in agonist-stimulated Gαq- Gαi2/3-protein coupling, IP3 generation, and ERK1/2-MAPK activation as compared to wild-type controls. Conversely, there was no difference in cell-surface density as well as ligand-binding properties of B2R and in efficiencies of cognate agonists at promoting B2R internalization and β2-arrestin recruitment. Importantly, both AltB2R and B2R proteins were overexpressed in prostate and breast cancers, compared with their normal counterparts suggesting new associative roles of AltB2R in these diseases. Our study shows that BDKRB2 is a dual-coding gene and identifies AltB2R as a novel positive modulator of some B2R signaling pathways. More broadly, it also supports a new, unexpected alternative proteome for GPCRs, which opens new frontiers in fields of GPCR biology, diseases and drug discovery.AAA+ proteins (ATPases Associated with diverse cellular Activities) are a superfamily of proteins that typically assemble into hexameric rings. These proteins contain AAA+ domains with two canonical motifs (Walker A and B) thatbind and hydrolyze ATP, allowing them to perform a wide variety of different functions. For example, AAA+ proteins play a prominent role in cellular proteostasis by controlling biogenesis, folding, trafficking, and degradation of proteins present within the cell. Several central proteolytic systems (e.g. Clp, Deg, FtsH, Lon, 26S proteasome) use AAA+ domains or AAA+ proteins to unfold protein substrates (using energy from ATP hydrolysis) to make them accessible for degradation. This allows AAA+ protease systems to degrade aggregates and large proteins, as well as smaller proteins, and feed them as linearized molecules into a protease chamber. This review provides an up-to-date and a comparative overview of the essential Clp AAA+ protease systems in cyanobacteria (e.g. Synechocystis spp), plastids of photosynthetic eukaryotes (e.g. Arabidopsis, Chlamydomonas) and apicoplasts in the non-photosynthetic apicomplexan pathogen Plasmodium falciparum. Recent progress and breakthroughs in identifying Clp protease structures, substrates, substrate adaptors (e.g. NblA/B, ClpS, ClpF), and degrons are highlighted. We comment on the physiological importance of Clp activity, including plastid biogenesis, proteostasis, the chloroplast Protein Unfolding Response (cpUPR) and metabolism across these diverse lineages. Outstanding questions as well as research opportunities and priorities to better understand the essential role of Clp systems in cellular proteostasis are discussed.
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