Candidate amino acids involved in H+ gating of acid-sensing ion channel 1a

Acid-sensing ion channels are ligand-gated cation channels, gated by extracellular H+. H+ is the simplest ligand possible, and whereas for larger ligands that gate ion channels complex binding sites in the three-dimensional structure of the proteins have to be assumed, H+ could in principle gate a channel by titration of a single amino acid. Experimental evidence suggests a more complex situation, however. For example, it has been shown that extracellular Ca2+ ions compete with H+; probably Ca2+ ions bound to the extracellular loop of ASICs stabilize the closed state of the channel and have to be displaced before the channel can open. In such a scheme, amino acids contributing to Ca2+ binding would also be candidates contributing to H+ gating. In this study we systematically screened more than 40 conserved, charged amino acids in the extracellular region of ASIC1a for a possible contribution to H+ gating. We identified four amino acids where substitution strongly affects H+ gating: Glu63, His72/His73, and Asp78. These amino acids are highly conserved among H+-sensitive ASICs and are candidates for the “H+ sensor” of ASICs

The large core limit of spiral waves in excitable media: A numerical approach

We modify the freezing method introduced by Beyn & Thuemmler, 2004, for analyzing rigidly rotating spiral waves in excitable media. The proposed method is designed to stably determine the rotation frequency and the core radius of rotating spirals, as well as the approximate shape of spiral waves in unbounded domains. In particular, we introduce spiral wave boundary conditions based on geometric approximations of spiral wave solutions by Archimedean spirals and by involutes of circles. We further propose a simple implementation of boundary conditions for the case when the inhibitor is non-diffusive, a case which had previously caused spurious oscillations. We then utilize the method to numerically analyze the large core limit. The proposed method allows us to investigate the case close to criticality where spiral waves acquire infinite core radius and zero rotation frequency, before they begin to develop into retracting fingers. We confirm the linear scaling regime of a drift bifurcation for the rotation frequency and the core radius of spiral wave solutions close to criticality. This regime is unattainable with conventional numerical methods.Comment: 32 pages, 17 figures, as accepted by SIAM Journal on Applied Dynamical Systems on 20/03/1

Different types of atrophy in the prostate with and without adenocarcinoma

OBJECTIVES: The purpose of this study was to evaluate, according to a classification proposed by a working group, the extent and type of atrophy lesions in radical prostatectomy specimens obtained from patients with prostatic carcinoma and benign prostatic hyperplasia (BPH), and to compare the prevalence and types of atrophy between two investigated groups. ----- METHODS: Histologic analysis of 1096 slides from 50 patients with carcinoma and 277 slides from 31 patients with BPH was performed to evaluate, according to the new prostatic atrophy classification, the number of foci and type of atrophic lesions. ----- RESULTS: Age, Gleason grade, and TNM showed no significant correlation with the number of proliferative atrophy (PA) and proliferative inflammatory atrophy (PIA) foci (p>0.05). PIA was significantly more frequent in prostates with carcinoma (1.63 vs 1.27 atrophic lesions per slide) (p<0.001), whereas PA displayed an increased frequency in BPH (2.28 vs 0.76 atrophic lesions per slide) (p<0.001). ----- CONCLUSIONS: We confirmed that PA and PIA are common findings in prostates with and without carcinoma, but the question of whether inflammation produces tissue damage and PA or whether some other insult induces the tissue damage and atrophy directly, with inflammation occurring secondarily, is still unresolved