Persistent thermal input controls steering behavior in Caenorhabditis elegans

Motile organisms actively detect environmental signals and migrate to a preferable environment. Especially, small animals convert subtle spatial difference in sensory input into orientation behavioral output for directly steering toward a destination, but the neural mechanisms underlying steering behavior remain elusive. Here, we analyze a C. elegans thermotactic behavior in which a small number of neurons are shown to mediate steering toward a destination temperature. We construct a neuroanatomical model and use an evolutionary algorithm to find configurations of the model that reproduce empirical thermotactic behavior. We find that, in all the evolved models, steering curvature are modulated by temporally persistent thermal signals sensed beyond the time scale of sinusoidal locomotion of C. elegans. Persistent rise in temperature decreases steering curvature resulting in straight movement of model worms, whereas fall in temperature increases curvature resulting in crooked movement. This relation between temperature change and steering curvature reproduces the empirical thermotactic migration up thermal gradients and steering bias toward higher temperature. Further, spectrum decomposition of neural activities in model worms show that thermal signals are transmitted from a sensory neuron to motor neurons on the longer time scale than sinusoidal locomotion of C. elegans. Our results suggest that employments of temporally persistent sensory signals enable small animals to steer toward a destination in natural environment with variable, noisy, and subtle cues.     

Detection of Peramivir and Laninamivir,New Anti-Influenza Drugs,in Sewage Effluent and River Waters in Japan

This is the first report of the detection of two new anti-influenza drugs, peramivir (PER) and laninamivir (LAN), in Japanese sewage effluent and river waters. Over about 1 year from October 2013 to July 2014, including the influenza prevalence season in January and February 2014, we monitored for five anti-influenza drugs—oseltamivir (OS), oseltamivir carboxylate (OC), zanamivir (ZAN), PER, and LAN—in river waters and in sewage effluent flowing into urban rivers of the Yodo River system in Japan. The dynamic profiles of these anti-influenza drugs were synchronized well with that of the numbers of influenza patients treated with the drugs. The highest levels in sewage effluents and river waters were, respectively, 82 and 41 ng/L (OS), 347 and 125 ng/L (OC), 110 and 35 ng/L (ZAN), 64 and 11 ng/L (PER), and 21 and 9 ng/L (LAN). However, application of ozone treatment before discharge from sewage treatment plants was effective in reducing the levels of these anti-influenza drugs in effluent. The effectiveness of the ozone treatment and the drug dependent difference in susceptibility against ozone were further evidenced by ozonation of a STP effluent in a batch reactor. These findings should help to promote further environmental risk assessment of the generation of drug-resistant influenza viruses in aquatic environments.     

Involvement of the Extrageniculate System in the Perception of Optical Illusions: A Functional Magnetic Resonance Imaging Study

Research on the neural processing of optical illusions can provide clues for understanding the neural mechanisms underlying visual perception. Previous studies have shown that some visual areas contribute to the perception of optical illusions such as the Kanizsa triangle and Müller-Lyer figure; however, the neural mechanisms underlying the processing of these and other optical illusions have not been clearly identified. Using functional magnetic resonance imaging (fMRI), we determined which brain regions are active during the perception of optical illusions. For our study, we enrolled 18 participants. The illusory optical stimuli consisted of many kana letters, which are Japanese phonograms. During the shape task, participants stated aloud whether they perceived the shapes of two optical illusions as being the same or not. During the word task, participants read aloud the kana letters in the stimuli. A direct comparison between the shape and word tasks showed activation of the right inferior frontal gyrus, left medial frontal gyrus, and right pulvinar. It is well known that there are two visual pathways, the geniculate and extrageniculate systems, which belong to the higher-level and primary visual systems, respectively. The pulvinar belongs to the latter system, and the findings of the present study suggest that the extrageniculate system is involved in the cognitive processing of optical illusions.     

Practical synthesis of precursor of [N-methyl-11C]vorozole, an efficient PET tracer targeting aromatase in the brain

A practical method to prepare precursor of [N-methyl-(11)C]vorozole ([(11)C]vorozole), an efficient positron emission tomography (PET) tracer for imaging aromatase in the living body, was established. Sufficient amount of the racemate including norvorozole, a demethylated vorozole derivative used as a precursor of [(11)C]vorozole, became available by means of high-yield eight-step synthesis. The enantiomers were separated by preparative HPLC using a chiral stationary phase column to give optically pure norvorozole and its enantiomer. From the latter, ent-[(11)C]vorozole, an enantiomer of [(11)C]vorozole, was prepared and used in the PET study for the first time, which was shown to bind very weakly to aromatase in rhesus monkey brain supporting the previous pharmacological results. The stable supply of norvorozole will facilitate further researches on aromatase in the living body including brain by the PET technique.     

Novel nonsecosteroidal vitamin D3 carboxylic acid analogs for osteoporosis, and SAR analysis

Novel vitamin D(3) analogs with carboxylic acid were explored, focusing on a nonsecosteroidal analog, LG190178, with a bisphenyl skeleton. From X-ray analysis of these analogs with vitamin D receptor (VDR), the carboxyl groups had very unique hydrogen bonding interactions in VDR and mimicked 1α-hydroxy group and/or 3β-hydroxy group of 1α,25-dihydroxyvitamin D(3). A highly potent analog, 6a, with good in vitro activity and pharmacokinetic profiles was identified from an SAR study. Compound 6a showed significant prevention of bone loss in a rat osteoporosis model by oral administration.     

Synthesis and structure-activity relationship of tricyclic carboxylic acids as novel anti-histamines

A series of tricyclic carboxylic acids having 6-amino-pyrimidine-2,4(1H,3H)-dione with piperazino or homopiperazino moiety linked by propylene, were synthesized and evaluated for their affinity toward human histamine H(1) receptor and Caco-2 cell permeability. Selected compounds were further evaluated for their oral anti-histaminic activity in mice, bioavailability in rats, and their anti-inflammatory activity in mice OVA-induced biphasic cutaneous reaction model. Among the compounds tested, dibenzoxazepine carboxylic acid 13b showed both histamine H(1) receptor antagonistic activity and anti-inflammatory activity in vivo. In addition, 13b exhibited low affinity toward α(1) receptor and low occupancy of H(1) receptor in the brain. It is therefore, believed that 13b is a potential candidate for development as 3rd generation anti-histamine.     

The genus Arctorthezia Cockerell (Hemiptera,Ortheziidae) with the description of a new species

This paper describes a new species of Arctorthezia Cockerell (Hemiptera: Coccoidea: Ortheziidae) from the Palaearctic region. The specimens were extracted from forest litter in the collections of Muséum d’histoire Naturelle de Genève, Switzerland, using Berlese funnels. Three further species, Arctorthezia cataphracta (Olafsen), Arctorthezia occidentalis (Douglas) and Arctorthezia pseudoccidentalis Morrison, are redescribed and re-illustrated. The genus Arctorthezia now contains five species. An identification key, diagnostic illustrations, photographs of unmounted females and new locality records of the Arctorthezia species currently known are provided.