CaMKII T286 phosphorylation has distinct essential functions in three forms of long-term plasticity

The Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) mediates long-term potentiation or depression (LTP or LTD) after distinct stimuli of hippocampal NMDA-type glutamate receptors (NMDARs). NMDAR-dependent LTD prevails in juvenile mice, but a mechanistically different form of LTD can be readily induced in adults by instead stimulating metabotropic glutamate receptors (mGluRs). However, the role that CaMKII plays in the mGluR-dependent form of LTD is not clear. Here we show that mGluR-dependent LTD also requires CaMKII and its T286 autophosphorylation (pT286), which induces Ca²⁺-independent autonomous kinase activity. In addition, we compared the role of pT286 among three forms of long-term plasticity (NMDAR-dependent LTP and LTD, and mGluR-dependent LTD) using simultaneous live imaging of endogenous CaMKII together with synaptic marker proteins. We determined that after LTP stimuli, pT286 autophosphorylation accelerated CaMKII movement to excitatory synapses. After NMDAR-LTD stimuli, pT286 was strictly required for any movement to inhibitory synapses. Similar to NMDAR-LTD, we found the mGluR-LTD stimuli did not induce CaMKII movement to excitatory synapses. However, in contrast to NMDAR-LTD, we demonstrate that the mGluR-LTD did not involve CaMKII movement to inhibitory synapses and did not require additional T305/306 autophosphorylation. Thus, despite its prominent role in LTP, we conclude that CaMKII T286 autophosphorylation is also required for both major forms of hippocampal LTD, albeit with differential requirements for the heterosynaptic communication of excitatory signals to inhibitory synapses.     

Protein restriction and branched‐chain amino acid restriction promote geroprotective shifts in metabolism

The proportion of humans suffering from age‐related diseases is increasing around the world, and creative solutions are needed to promote healthy longevity. Recent work has clearly shown that a calorie is not just a calorie—and that low protein diets are associated with reduced mortality in humans and promote metabolic health and extended lifespan in rodents. Many of the benefits of protein restriction on metabolism and aging are the result of decreased consumption of the three branched‐chain amino acids (BCAAs), leucine, isoleucine, and valine. Here, we discuss the emerging evidence that BCAAs are critical modulators of healthy metabolism and longevity in rodents and humans, as well as the physiological and molecular mechanisms that may drive the benefits of BCAA restriction. Our results illustrate that protein quality—the specific composition of dietary protein—may be a previously unappreciated driver of metabolic dysfunction and that reducing dietary BCAAs may be a promising new approach to delay and prevent diseases of aging.     

Tree House Explorer: A Novel Genome Browser for Phylogenomics

Tree House Explorer (THEx) is a genome browser that integrates phylogenomic data and genomic annotations into a single interactive platform for combined analysis. THEx allows users to visualize genome-wide variation in evolutionary histories and genetic divergence on a chromosome-by-chromosome basis, with continuous sliding window comparisons to gene annotations, recombination rates, and other user-specified, highly customizable feature annotations. THEx provides a new platform for interactive phylogenomic data visualization to analyze and interpret the diverse evolutionary histories woven throughout genomes. Hosted on Conda, THEx integrates seamlessly into new or pre-existing workflows.     

Etude ultrastructurale d'images de fonte holocrine dans la cortico-surrenale

Conclusion La présence d'un phénomène dégénératif dans les couches profondes de la cortico-surrénale de 12 animaux normaux donne à penser qu'il existe dans cette glande un mécanisme physiologique de fonte holocrine. Cette idée est appuyée sur des images de passage de débris cellulaires dans la lumière des vaisseaux. L'influence qui détermine de telles modifications des cellules glandulaires reste à préciser. Ce sera l'objet d'une étude expérimentale en cours d'exécution.     

Cloning of the lkyB (tolB) gene of Escherichia coli K12 and characterization of its product

Summary The lkyB gene of Escherichia coli K12 has been cloned from the Clarke and Carbon colony bank by selecting a ColE1 plasmid conferring cholic acid resistance to lkyB mutants. The lkyB gene was localized on hybrid plasmid pJC778 by analysis of mutated plasmids generated by Tn5 insertions. Restriction analysis and complementation studies indicated that plasmid pJC778 carried genes nadA, lkyB and sucA which mapped at min 16.5; the lkyB ⁺ allele was dominant over the lkyB207 mutant allele. Analysis of cell envelope proteins from strains carrying plasmids pJC778 (lkyB ⁺), pJC2578 or pJC2579 (lkyB::Tn5), as well as plasmid-coded proteins in a maxicell system, made it likely that the lkyB gene product was a membrane protein of molecular weight 42,000.