Characterization of skeletal phenotypes of TRα1(PV) and TRβ(PV) mutant mice: implications for tissue thyroid status and T3 target gene expression

Bone development is extremely sensitive to alterations in thyroid status. Recently, we analyzed the skeletal phenotypes of mice with the dominant negative resistance to thyroid hormone (RTH) mutation PV targeted to either the thyroid hormone receptor (TR) α1 or β gene. This perspective summarizes our findings to date and explores the wider implications for thyroid status and T3 target gene expression in individual tissues

Back Reaction And Local Cosmological Expansion Rate

We calculate the back reaction of cosmological perturbations on a general relativistic variable which measures the local expansion rate of the Universe. Specifically, we consider a cosmological model in which matter is described by a single field. We analyze back reaction both in a matter dominated Universe and in a phase of scalar field-driven chaotic inflation. In both cases, we find that the leading infrared terms contributing to the back reaction vanish when the local expansion rate is measured at a fixed value of the matter field which is used as a clock, whereas they do not appear to vanish if the expansion rate is evaluated at a fixed value of the background time. We discuss possible implications for more realistic models with a more complicated matter sector.Comment: 7 pages, No figure

Chaos and Preheating

We show evidence for a relationship between chaos and parametric resonance both in a classical system and in the semiclassical process of particle creation. We apply our considerations in a toy model for preheating after inflation.Comment: 7 pages, 9 figures; uses epsfig and revtex v3.1. Matches version accepted for publication in Phys. Rev.

Cosmic microwave background and parametric resonance in reheating

The variation of the perturbative 3-curvature parameter, \zeta, is investigated in the period of reheating after inflation. The two-field model used has the inflaton, with an extra scalar field coupled to it, and non-linear effects of both fields are included as well as a slow decay mechanism into the hydrodynamic fluid of the radiation era. Changes in \zeta occur and persist into the succeeding cosmic eras to influence the generation of the cosmic microwave background fluctuations.Comment: 21 pages, 6 figures.Corrects misprinted formula and 2 number

An Assessment of the Use of Chimpanzees in Hepatitis C Research Past, Present and Future: 1. Validity of the Chimpanzee Model

The USA is the only significant user of chimpanzees in biomedical research in the world, since many countries have banned or limited the practice due to substantial ethical, economic and scientific concerns. Advocates of chimpanzee use cite hepatitis C research as a major reason for its necessity and continuation, in spite of supporting evidence that is scant and often anecdotal. This paper examines the scientific and ethical issues surrounding chimpanzee hepatitis C research, and concludes that claims of the necessity of chimpanzees in historical and future hepatitis C research are exaggerated and unjustifiable, respectively. The chimpanzee model has several major scientific, ethical, economic and practical caveats. It has made a relatively negligible contribution to knowledge of, and tangible progress against, the hepatitis C virus compared to non-chimpanzee research, and must be considered scientifically redundant, given the array of alternative methods of inquiry now available. The continuation of chimpanzee use in hepatitis C research adversely affects scientific progress, as well as chimpanzees and humans in need of treatment. Unfounded claims of its necessity should not discourage changes in public policy regarding the use of chimpanzees in US laboratories

Gravitational collapse of a Hagedorn fluid in Vaidya geometry

The gravitational collapse of a high-density null charged matter fluid, satisfying the Hagedorn equation of state, is considered in the framework of the Vaidya geometry. The general solution of the gravitational field equations can be obtained in an exact parametric form. The conditions for the formation of a naked singularity, as a result of the collapse of the compact object, are also investigated. For an appropriate choice of the arbitrary integration functions the null radial outgoing geodesic, originating from the shell focussing central singularity, admits one or more positive roots. Hence a collapsing Hagedorn fluid could end either as a black hole, or as a naked singularity. A possible astrophysical application of the model, to describe the energy source of gamma-ray bursts, is also considered.Comment: 14 pages, 2 figures, to appear in Phys. Rev.

Inflation and late time acceleration in braneworld cosmological models with varying brane tension

Braneworld models with variable brane tension $\lambda$ introduce a new degree of freedom that allows for evolving gravitational and cosmological constants, the latter being a natural candidate for dark energy. We consider a thermodynamic interpretation of the varying brane tension models, by showing that the field equations with variable $\lambda$ can be interpreted as describing matter creation in a cosmological framework. The particle creation rate is determined by the variation rate of the brane tension, as well as by the brane-bulk energy-matter transfer rate. We investigate the effect of a variable brane tension on the cosmological evolution of the Universe, in the framework of a particular model in which the brane tension is an exponentially dependent function of the scale factor. The resulting cosmology shows the presence of an initial inflationary expansion, followed by a decelerating phase, and by a smooth transition towards a late accelerated de Sitter type expansion. The varying brane tension is also responsible for the generation of the matter in the Universe (reheating period). The physical constraints on the model parameters, resulted from the observational cosmological data, are also investigated.Comment: 25 pages, 8 figures, accepted for publication in European Physical Journal

Gravitational Fermion Production in Inflationary Cosmology

We revisit the gravitational production of massive Dirac fermions in inflationary cosmology with a focus on clarifying the analytic computation of the particle number density in both the large and the small mass regimes. For the case in which the masses of the gravitationally produced fermions are small compared to the Hubble expansion rate at the end of inflation, we obtain a universal result for the number density that is nearly independent of the details of the inflationary model. The result is identical to the case of conformally coupled scalars up to an overall multiplicative factor of order unity for reasons other than just counting the fermionic degrees of freedom.Comment: 21 pages, 1 figur

A mouse model with a frameshift mutation in the nuclear factor I/X (NFIX) gene has phenotypic features of Marshall-Smith Syndrome

The nuclear factor I/X (NFIX) gene encodes a ubiquitously expressed transcription factor whose mutations lead to two allelic disorders characterized by developmental, skeletal, and neural abnormalities, namely, Malan syndrome (MAL) and Marshall–Smith syndrome (MSS). NFIX mutations associated with MAL mainly cluster in exon 2 and are cleared by nonsense-mediated decay (NMD) leading to NFIX haploinsufficiency, whereas NFIX mutations associated with MSS are clustered in exons 6–10 and escape NMD and result in the production of dominant-negative mutant NFIX proteins. Thus, different NFIX mutations have distinct consequences on NFIX expression. To elucidate the in vivo effects of MSS-associated NFIX exon 7 mutations, we used CRISPR-Cas9 to generate mouse models with exon 7 deletions that comprised: a frameshift deletion of two nucleotides (Nfix Del2); in-frame deletion of 24 nucleotides (Nfix Del24); and deletion of 140 nucleotides (Nfix Del140). Nfix+/Del2, Nfix+/Del24, Nfix+/Del140, NfixDel24/Del24, and NfixDel140/Del140 mice were viable, normal, and fertile, with no skeletal abnormalities, but NfixDel2/Del2 mice had significantly reduced viability (p < 0.002) and died at 2–3 weeks of age. Nfix Del2 was not cleared by NMD, and NfixDel2/Del2 mice, when compared to Nfix+/+ and Nfix+/Del2 mice, had: growth retardation; short stature with kyphosis; reduced skull length; marked porosity of the vertebrae with decreased vertebral and femoral bone mineral content; and reduced caudal vertebrae height and femur length. Plasma biochemistry analysis revealed NfixDel2/Del2 mice to have increased total alkaline phosphatase activity but decreased C-terminal telopeptide and procollagen-type-1-N-terminal propeptide concentrations compared to Nfix+/+ and Nfix+/Del2 mice. NfixDel2/Del2 mice were also found to have enlarged cerebral cortices and ventricular areas but smaller dentate gyrus compared to Nfix+/+ mice. Thus, NfixDel2/Del2 mice provide a model for studying the in vivo effects of NFIX mutants that escape NMD and result in developmental abnormalities of the skeletal and neural tissues that are associated with MSS