Bent dsDNA with defined geometric characteristics in terms of complexes of bridged oligonucleotides

An opportunity of designing nontypical double-stranded DNA structures containing nonnatural inserts in a regular nucleotide DNA sequence has been investigated. The looped nucleotide inserts on the basis of adenylates and thymidilates, and nonnucleotide inserts on the basis of phosphodiesters of diethyleneglycol, 1,10-decanediol, and 3-hydroxy-2(hydroxymethyl)tetrahydrofuran were introduced into the backbone of a 32-mer native DNA duplex. These inserts formed the internal loops in the modified double-stranded DNA fragments which were shown to lead to bending of the linear duplex structure by 16 to 83 degrees. The dependencies of the bend angle of dsDNA on the composition and the length of the looped regions were determined. It was established that the bend of the irregular region of dsDNA depended on the electrostatic interaction of the phosphate residues. The tension in the complex structure could be reduced by the introduction of additional nucleotide units opposite the loop, which led to some relaxation of the bent helix. The resulting parameters of the bend values were shown to be in a good agreement with the published data obtained by NMR spectroscopy. It was demonstrated that the variation of the nature or the length of the insert allowed one to regulate the level of the local perturbation of the duplex structure and, thereby, influence both the bend level of the double helix and the destabilization of the modified complex.     

The Eco-epidemiology of Pacific Coast Tick Fever in California

Rickettsia philipii (type strain “Rickettsia 364D”), the etiologic agent of Pacific Coast tick fever (PCTF), is transmitted to people by the Pacific Coast tick, Dermacentor occidentalis. Following the first confirmed human case of PCTF in 2008, 13 additional human cases have been reported in California, more than half of which were pediatric cases. The most common features of PCTF are the presence of at least one necrotic lesion known as an eschar (100%), fever (85%), and headache (79%); four case-patients required hospitalization and four had multiple eschars. Findings presented here implicate the nymphal or larval stages of D. occidentalis as the primary vectors of R. philipii to people. Peak transmission risk from ticks to people occurs in late summer. Rickettsia philipii DNA was detected in D. occidentalis ticks from 15 of 37 California counties. Similarly, non-pathogenic Rickettsia rhipicephali DNA was detected in D. occidentalis in 29 of 38 counties with an average prevalence of 12.0% in adult ticks. In total, 5,601 ticks tested from 2009 through 2015 yielded an overall R. philipii infection prevalence of 2.1% in adults, 0.9% in nymphs and a minimum infection prevalence of 0.4% in larval pools. Although most human cases of PCTF have been reported from northern California, acarological surveillance suggests that R. philipii may occur throughout the distribution range of D. occidentalis.     

Effects of chorda tympani nerve anesthesia on taste responses in the NST

Human clinical and psychophysical observations suggest that the taste system is able to compensate for losses in peripheral nerve input, since patients do not commonly report decrements in whole mouth taste following chorda tympani nerve damage or anesthesia. Indeed, neurophysiological data from the rat nucleus of the solitary tract (NST) suggests that a release of inhibition (disinhibition) may occur centrally following chorda tympani nerve anesthesia. Our purpose was to study this possibility further. We recorded from 59 multi- and single- unit taste-responsive sites in the rat NST before, during and after recovery from chorda tympani nerve anesthesia. During anesthesia, average anterior tongue responses were eliminated but no compensatory increases in palatal or posterior tongue responses were observed. However, six individual sites displayed increased taste responsiveness during anesthesia. The average increase was 32.9%. Therefore, disinhibition of taste responses was observed, but infrequently and to a small degree in the NST At a subset of sites, chorda tympani-mediated responses decreased while greater superficial petrosal-mediated responses remained the same during anesthesia. Since this effect was accompanied by a decrease in spontaneous activity, we propose that taste compensation may result in part by a change in signal-to-noise ratio at a subset of sites.