Prolonged day length exposure improves circadian deficits and survival in a transgenic mouse model of Huntington's disease

The circadian disruption seen in patients of Huntington's disease (HD) is recapitulated in the R6/2 mouse model. As the disease progresses, the activity of R6/2 mice increases dramatically during the rest (light) period and decreases during the active (dark) period, eventually leading to a complete disintegration of rest-activity rhythms by the age of ~16 weeks. The suprachiasmatic nucleus controls circadian rhythms by entraining the rest-activity rhythms to the environmental light-dark cycle. Since R6/2 mice can shift their rest-activity rhythms in response to a jet-lag paradigm and also respond positively to bright light therapy (1000 lx), we investigated whether or not a prolonged day length exposure could reduce their daytime activity and improve their behavioural circadian rhythms. We found that a long-day photoperiod (16 h light/8 h dark cycle; 100 lx) significantly improved the survival of R6/2 female mice by 2.4 weeks, compared to mice kept under standard conditions (12 h light/12 h dark cycle). Furthermore, a long-day photoperiod improved the nocturnality of R6/2 female mice. Mice kept under long-day photoperiod also maintained acrophase in activity rhythms (a parameter of rhythmicity strength) in phase with that of WT mice, even if they were symptomatic. By contrast, a short-day photoperiod (8 h light/16 h dark cycle) was deleterious to R6/2 female mice and further reduced the survival by ~1 week. Together, our results support the idea that light therapy may be beneficial for improving circadian dysfunction in HD patients.This research was supported by a grant from CHDIInc

Sustainability of multi-field inflation and bound on string scale

We study the effects of the interaction terms between the inflaton fields on the inflationary dynamics in multi-field models. With power law type potential and interactions, the total number of e-folds may get considerably reduced and can lead to unacceptably short period of inflation. Also we point out that this can place a bound on the characteristic scale of the underlying theory such as string theory. Using a simple multi-field chaotic inflation model from string theory, the string scale is constrained to be larger than the scale of grand unified theory.Comment: (v1) 9 pages, 1 figure;(v2) 10 pages, references added; (v3) 15 pages, 4 figures, more discussions about parameters and observable quantities, references added, to appear in Modern Physics Letters

A covariant approach to general field space metric in multi-field inflation

We present a covariant formalism for general multi-field system which enables us to obtain higher order action of cosmological perturbations easily and systematically. The effects of the field space geometry, described by the Riemann curvature tensor of the field space, are naturally incorporated. We explicitly calculate up to the cubic order action which is necessary to estimate non-Gaussianity and present those geometric terms which have not yet known before.Comment: (v1) 18 pages, 1 figure; (v2) references added, typos corrected, to appear in Journal of Cosmology and Astroparticle Physics; (v3) typos in (54), (62) and (64) correcte

Radiocarbon dates from jar and coffin burials of the Cardamom Mountains reveal a unique mortuary ritual in Cambodia's late- to post-Angkor period (15th-17th centuries AD)

We present the first radiocarbon dates from previously unrecorded, secondary burials in the Cardamom Mountains, Cambodia. The mortuary ritual incorporates nautical tradeware ceramic jars and log coffins fashioned from locally harvested trees as burial containers, which were set out on exposed rock ledges at 10 sites in the eastern Cardamom Massif. The suite of 28 14C ages from 4 of these sites (Khnorng Sroal, Phnom Pel, Damnak Samdech, and Khnang Tathan) provides the first estimation of the overall time depth of the practice. The most reliable calendar date ranges from the 4 sites reveals a high- land burial ritual unrelated to lowland Khmer culture that was practiced from cal AD 1395 to 1650. The time period is concurrent with the 15th century decline of Angkor as the capital of the Khmer kingdom and its demise about AD 1432, and the subsequent shift of power to new Mekong trade ports such as Phnom Penh, Udong, and Lovek. We discuss the Cardamom ritual relative to known funerary rituals of the pre to post-Angkorian periods, and to similar exposed jar and coffin burial rituals in Mainland and Island Southeast Asia

Non-Gaussianity from false vacuum inflation: Old curvaton scenario

We calculate the three-point correlation function of the comoving curvature perturbation generated during an inflationary epoch driven by false vacuum energy. We get a novel false vacuum shape bispectrum, which peaks in the equilateral limit. Using this result, we propose a scenario which we call "old curvaton". The shape of the resulting bispectrum lies between the local and the false vacuum shapes. In addition we have a large running of the spectral index.Comment: 13 pages, 3 figures; v2 with minor revison; v3 final version to appear on JCA

From the Spectrum to Inflation : An Inverse Formula for the General Slow-Roll Spectrum

We propose a general inverse formula for extracting inflationary parameters from the observed power spectrum of cosmological perturbations. Under the general slow-roll scheme, which helps to probe the properties of inflation in a model independent way, we invert the leading order, single field, power spectrum formula. We also give some physically interesting examples to demonstrate its wide applicability and illuminate its properties.Comment: 8 pages, no figure ; References expande

Sublingual Immunization with M2-Based Vaccine Induces Broad Protective Immunity against Influenza

The ectodomain of matrix protein 2 (M2e) of influenza A virus is a rationale target antigen candidate for the development of a universal vaccine against influenza as M2e undergoes little sequence variation amongst human influenza A strains. Vaccine-induced M2e-specific antibodies (Abs) have been shown to display significant cross-protective activity in animal models. M2e-based vaccine constructs have been shown to be more protective when administered by the intranasal (i.n.) route than after parenteral injection. However, i.n. administration of vaccines poses rare but serious safety issues associated with retrograde passage of inhaled antigens and adjuvants through the olfactory epithelium. In this study, we examined whether the sublingual (s.l.) route could serve as a safe and effective alternative mucosal delivery route for administering a prototype M2e-based vaccine. The mechanism whereby s.l. immunization with M2e vaccine candidate induces broad protection against infection with different influenza virus subtypes was explored.A recombinant M2 protein with three tandem copies of the M2e (3M2eC) was expressed in Escherichia coli. Parenteral immunizations of mice with 3M2eC induced high levels of M2e-specific serum Abs but failed to provide complete protection against lethal challenge with influenza virus. In contrast, s.l. immunization with 3M2eC was superior for inducing protection in mice. In the latter animals, protection was associated with specific Ab responses in the lungs.The results demonstrate that s.l. immunization with 3M2eC vaccine induced airway mucosal immune responses along with broad cross-protective immunity to influenza. These findings may contribute to the understanding of the M2-based vaccine approach to control epidemic and pandemic influenza infections