Signaling by the integrated stress response kinase PKR is fine-tuned by dynamic clustering

The double-stranded RNA sensor kinase PKR is one of four integrated stress response (ISR) sensor kinases that phosphorylate the α subunit of eukaryotic initiation factor 2 (eIF2α) in response to stress. The current model of PKR activation considers the formation of back-to-back PKR dimers as a prerequisite for signal propagation. Here we show that PKR signaling involves the assembly of dynamic PKR clusters. PKR clustering is driven by ligand binding to PKR’s sensor domain and by front-to-front interfaces between PKR’s kinase domains. PKR clusters are discrete, heterogeneous, autonomous coalescences that share some protein components with processing bodies. Strikingly, eIF2α is not recruited to PKR clusters, and PKR cluster disruption enhances eIF2α phosphorylation. Together, these results support a model in which PKR clustering may limit encounters between PKR and eIF2α to buffer downstream signaling and prevent the ISR from misfiring.     

Numerical simulations of hydra head regeneration using a proportion-regulating version of the Gierer-Meinhardt model

The results of a wide variety of transplantation experiments with Hydra, including experiments on animals in various stages of head regeneration, can be accounted for in a quantitatively satisfactory way with a reaction-diffusion model. This model, a proportion-regulating version of the Gierer-Meinhardt model, also accounts for the observed allometry of the head in Hydra. Values can be derived for all nine of the independent parameters of the model using eleven experimental results, and the model with these parameter values predicts the results of six further experiments.     

Herbicide resistance—what have we learned from other disciplines?

Herbicide resistance is a growing threat to agriculture and has parallels to resistances to fungicides and insecticides. However, there are many reasons to treat the resistance to herbicides differently. To highlight these similarities and differences, three pests, a weed, an insect, and a disease that have shown the ability to rapidly develop resistance to a variety of products and product classes were used as illustrations. The situation in herbicide resistance is approaching a point already experienced by the other pest control disciplines, and thus, it is worthwhile to revisit their experiences.     

Time course of airway remodelling after an acute chlorine gas exposure in mice

Accidental chlorine (Cl₂) gas inhalation is a common cause of acute airway injury. However, little is known about the kinetics of airway injury and repair after Cl₂ exposure. We investigated the time course of airway epithelial damage and repair in mice after a single exposure to a high concentration of Cl₂ gas. Mice were exposed to 800 ppm Cl₂ gas for 5 minutes and studied from 12 hrs to 10 days post-exposure. The acute injury phase after Cl₂ exposure (≤ 24 hrs post-exposure) was characterized by airway epithelial cell apoptosis (increased TUNEL staining) and sloughing, elevated protein in bronchoalveolar lavage fluid, and a modest increase in airway responses to methacholine. The repair phase after Cl₂ exposure was characterized by increased airway epithelial cell proliferation, measured by immunoreactive proliferating cell nuclear antigen (PCNA), with maximal proliferation occurring 5 days after Cl₂ exposure. At 10 days after Cl₂ exposure the airway smooth muscle mass was increased relative to controls, suggestive of airway smooth muscle hyperplasia and there was evidence of airway fibrosis. No increase in goblet cells occurred at any time point. We conclude that a single exposure of mice to Cl₂ gas causes acute changes in lung function, including pulmonary responsiveness to methacholine challenge, associated with airway damage, followed by subsequent repair and airway remodelling.     

Bacteriophage lambda-E. coli K12 vector-host system for gene cloning and expression under lactose promoter control. II. DNA fragment insertion at the vicinity of the lac UV5 promoter.

Summary Recombinant plasmids containing the entire 16S RNA gene from the rrn B cistron of E. coli inserted in Col E1 and pBR322 plasmid vectors have been constructed. These plasmids have been mapped using several restriction endonucleases as well as by DNA-RNA hybridization. These maps reveal previously undetected restriction sites in the rrn B cistron and in Col E1 plasmid DNA.