In the 2016/2017 winter season in Japan, HuNoV GII.P16-GII.2 strains (2016 strains) emerged and caused large outbreaks of acute gastroenteritis. To better understand the outbreaks, we examined the molecular evolution of the VP1 gene and RdRp region in 2016 strains from patients by studying their time-scale evolutionary phylogeny, positive/negative selection, conformational epitopes, and phylodynamics. The time-scale phylogeny suggested that the common ancestors of the 2016 strains VP1 gene and RdRp region diverged in 2006 and 1999, respectively, and that the 2016 strain was the progeny of a pre-2016 GII.2. The evolutionary rates of the VP1 gene and RdRp region were around 10-3 substitutions/site/year. Amino acid substitutions (position 341) in an epitope in the P2 domain of 2016 strains were not found in pre-2016 GII.2 strains. Bayesian skyline plot analyses showed that the effective population size of the VP1 gene in GII.2 strains was almost constant for those 50 years, although the number of patients with NoV GII.2 increased in 2016. The 2016 strain may be involved in future outbreaks in Japan and elsewhere.
CorrectionsNEUROBIOLOGY. For the article ''Coupling between changes in human brain temperature and oxidative metabolism during prolonged visual stimulation'' by Dmitriy A. Yablonskiy, Joseph J. H. Ackerman, and Marcus E. Raichle, which appeared in number 13, June 20, 2000, of Proc. Natl. Acad. Sci. USA (97, 7603-7608), the authors note a correction in the second to last paragraph on page 7604. The sentence ''It is well known from positron-emission tomography (PET) data (17, 18) that rCMRO 2 maps in the normal human brain are largely flat despite considerable regional differences in rCBF and rCMRO 2 maps'' should read: ''It is well known from positron-emission tomography (PET) data (17,18) MAP2), which was increased more than 8-fold after copolymerization of MAP2 with tubulin. Finally, steroid effects on microtubule-assembly kinetics were assayed. Pregnenolone induced a large, dose-related increase of both the rate and extent of MAP2-induced tubulin assembly, whereas progesterone, inactive per se, counteracted the stimulatory effect of pregnenolone. Electron microscopic analysis confirmed that pregnenolone-increased assembly of microtubules produced a completely normal structure. The stimulatory effect on MAP2-tubulin interaction was also observed in fetal rat-brain neuron cultures. Therefore, we propose a mechanism of neurosteroid action, the control of microtubule or, more generally, of neural cytoskeleton dynamics, with potential roles in brain development, plasticity, and aging.T he characterization of pregnenolone (PREG) and of dehydroepiandrosterone (DHEA) in the rat brain as nonconjugated steroids and their sulfate and fatty acid esters has led to the discovery of a steroid biosynthetic pathway in the central nervous system. Nongenomic, membrane receptor-mediated activities have been documented for PREG sulfate (PREGS) and DHEA sulfate (DHEAS). They are prototypic, naturally excitatory neurosteroids, because at low-micromolar concentrations, they antagonize ␥-aminobutyric acid type A receptors or potentiate glutamate receptors of the N-methyl-D-aspartate type, and they may modulate other neurotransmitter receptors (1-3).However, no intracellular binding protein has been reported so far in the nervous system for DHEA or PREG. In this paper, we have investigated PREG binding sites in rat-brain cytosol. The search for potential binding proteins in cytosol preparations led to the discovery of a PREG binding site on microtubuleassociated protein 2 (MAP2), which has important roles in the nervous system.Neurons have a characteristic morphology of neuritic processes densely filled with parallel arrays of microtubules, which play an essential role in the growth and maintenance of neurites during neuronal differentiation (4, 5). Neuronal microtubules are composed of tubulin and of several nontubulin proteins that purify with tubulin throughout several courses of polymerization-depolymerization (6). The proteins present in in vitropolymerized microtubules from brain extracts have been characterized. Tubulin is a pro...
We study light-cone gauge string field theory in noncritical space-time dimensions. Such a theory corresponds to a string theory in a Lorentz noninvariant background. We identify the worldsheet theory for the longitudinal coordinate variables X ± and study its properties. It is a CFT with the right value of Virasoro central charge, using which we propose a BRST invariant formulation of the worldsheet theory.
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