In this issue

You give me fever all through the night... Peggy Lee probably wasn't singing about Q fever, a severe but self‐limiting flu‐like disease in humans caused by Coxiella burnetii . It also infects a wide variety of wild and domesticated animals. Although it is an obligate intracellular organism, it is environmentally rather stable, resistant to many decontamination methods and a potential bio‐warfare agent. Commercial diagnostic tests (complement fixation, indirect immunofluorescence) require purified organisms as antigens. Vigil et al. applied in vitro transcription/translation to generate proteins and peptides representing >80% of the ORFs of the bacterial proteome. Probing arrayed proteins with infected patient sera yielded 21 reactive antigens, 13 significantly above controls. An additional 64 were too variable until validated further. Nine of those were potential diagnostic tools or subunit vaccine candidates. pp. 2259–2269HSA: hides secret association with protease? How does a cancer cell create a serum signal peptide in the midst of the huge masses of HSA that circulate continuously? Dekker et al. propose here a proteolytic method for metastasizing prostate tumors that leverages the mass of HSA in creating the signal. The proteases did it! Looking carefully at the termini and sequences of the peptides that correlated with the upregulation of mass spec‐detected peptides, the researchers found that many of the indicator fragments were HSA fragments and did not exhibit trypsin termini after a tryptic digestion. This also holds true for synthetic peptides, which worked quite well as substrates, with digestion sometimes running more than 95%. Protease inhibitor cocktail reduced the activity substantially. Now the question is how to associate the diseases with peptides and peptidases, reputed to constitute 2% of the human genome. pp. 2348–2358ADding up Alzheimer amyloid precursor protein interactions Sorting out the protein interactions (PPI) of amyloid precursor protein (APP) is complicated by the sheer number of processing steps APP might be involved in. Perreau et al. took up the challenge because APP is postulated to be the precursor of Aβ, the primary element of Alzheimer's plaques. Initial attempts using high‐throughput methodology were plagued with false positives. Careful curation of published studies of APP and Ab yielded a network that extended in places to binding domain level. Analyzing the network that resulted and gene ontology patterns identified interesting, potentially novel relationships not previously seen. Particularly interesting is the finding that some of the soluble peptides are released extracellularly where they interact with the CNTN1 subnetwork and the prion protein (PRNP). Another surprise is the apparent role APP plays in wound healing by modulation of A. pp. 2377–2395