AAA+ Protein-Based Technologies to Counter Neurodegenerative Disease

Protein misfolding and overloaded proteostasis networks underlie a range of neurodegenerative diseases. No cures exist for these diseases, but developing effective therapeutic agents targeting the toxic, misfolded protein species in disease is one promising strategy. AAA+ (ATPases associated with diverse cellular activities) protein translocases, which naturally unfold and translocate substrate proteins, could be potent therapeutic agents to disassemble toxic protein conformers in neurodegenerative disease. Here, we discuss repurposing AAA+ protein translocases Hsp104 and proteasome-activating nucleotidase (PAN) to alleviate the toxicity from protein misfolding in neurodegenerative disease. Hsp104 effectively protects various animal models from neurodegeneration underpinned by protein misfolding, and enhanced Hsp104 variants strongly counter neurodegenerative disease-associated protein misfolding toxicity in yeast, Caenorhabditis elegans, and mammalian cells. Similarly, a recently engineered PAN variant (PAN^et) mitigates photoreceptor degeneration instigated by protein misfolding in a mouse model of retinopathy. Further study and engineering of AAA+ translocases like Hsp104 and PAN will reveal promising agents to combat protein misfolding toxicity in neurodegenerative disease.     

Determination of steroid hormones in whale blow: It is possible

The feasibility of using analysis of hormone content of whale blow samples to assess reproductive function is addressed. A suitable collection method and analytical technique using liquid chromatography-mass spectrometry (LC-MS) has been developed. Blow samples were collected opportunistically from free-ranging humpback whales ( Megaptera novaeangliae ) ( n = 35) and North Atlantic right whales ( Eubalaena glacialis ) ( n = 18) using a 13-m carbon fiber pole with a collection device. Samples were analyzed for the presence of testosterone and progesterone using a 55% isocratic gradient with LC-MS. Testosterone was detected in four humpback whale samples and eight northern right whale samples. Progesterone was detected in seven humpback whale samples and eight northern right whale samples. This is the first documented use of lung mucosa to determine the presence of reproductive hormones in any free-swimming cetacean and may provide a novel non-invasive technique to quantify the hormonal condition of free-swimming animals that spend brief periods of time at the water's surface.     

Correction to: First description of a sex segregated aggregation of silky sharks (Carcharhinus falciformis) and the frequency and distribution of mating wounds off the tip of the Baja California Peninsula

Environmental Biology of Fishes -     

Fast atom bombardment mass spectrometry and tandem mass spectrometry in antibiotics: identification of nucleoside antitumor antibiotic toyocamycin in fermentation broth

The presence of the nucleoside antitumor antibiotic toyocamycin in the fermentation broth was determined by a combination of negative and positive ion fast atom bombardment (FAB) mass spectrometry, high resolution FAB mass spectrometry and mass-analysed ion kinetic energy spectrometry (MIKES). A reasonable limit of detection for toyocamycin in the whole broth was obtained by combining the specificity of mass spectrometry/mass spectrometry (also called tandem mass spectrometry) to FAB. The role played by the fermentation matrix upon the production and the observation of characteristic ions by FAB using xenon atoms was examined. High-performance liquid chromatography (HPLC) and FAB mass spectrometry were used to monitor toyocamycin at all stages of strain development, fermentation and recovery.