Neutrino masses in quartification schemes

The idea of quark-lepton universality at high energies has recently been explored in unified theories based upon the quartification gauge group SU(3)^4. These schemes encompass a quark-lepton exchange symmetry that results upon the introduction of leptonic colour. It has been demonstrated that in models in which the quartification gauge symmetry is broken down to the standard model gauge group, gauge coupling constant unification can be achieved, and there is no unique scenario. The same is also true when the leptonic colour gauge group is only partially broken, leaving a remnant SU(2)_\ell symmetry at the standard model level. Here we perform an analysis of the neutrino mass spectrum of such models. We show that these models do not naturally generate small Majorana neutrino masses, thus correcting an error in our earlier quartification paper, but with the addition of one singlet neutral fermion per family there is a realisation of see-saw suppressed masses for the neutrinos. We also show that these schemes are consistent with proton decay.Comment: 12 pages, minor changes. To appear in Phys. Rev.

Generating extremal neutrino mixing angles with Higgs family symmetries

The existence of maximal and minimal mixing angles in the neutrino mixing matrix motivates the search for extensions to the Standard Model that may explain these angles. A previous study (C.I.Low and R.R.Volkas, Phys.Rev.D68,033007(2003)), began a systematic search to find the minimal extension to the Standard Model that explains these mixing angles. It was found that in the minimal extensions to the Standard Model which allow neutrino oscillations, discrete unbroken lepton family symmetries only generate neutrino mixing matrices that are ruled out by experiment. This paper continues the search by investigating all models with two or more Higgs doublets, and an Abelian family symmetry. It is found that discrete Abelian family symmetries permit, but cannot explain, maximal atmospheric mixing, however these models can ensure theta_{13}=0.Comment: Minor modifications, references added, typos corrected. LaTeX, 16 page

Abelian family symmetries and the simplest models that give theta13=0 in the neutrino mixing matrix

I construct predictive models of neutrino mass and mixing that have fewer parameters, both in the lepton sector and overall, than the default seesaw model. The predictions are theta13=0 and one massless neutrino, with the models having a Z4 or Z2 symmetry and just one extra degree of freedom: one real singlet Higgs field. It has been shown that models with an unbroken family symmetry, and with no Higgs fields other than the Standard Model Higgs doublet produce masses and mixing matrices that have been ruled out by experiment. Therefore, this article investigates the predictions of models with Abelian family symmetries that involve Higgs singlets, doublets and triplets, in the hope that they may produce the maximal and minimal mixing angles seen in the best fit neutrino mixing matrix. I demonstrate that these models can only produce mixing angles that are zero, maximal or unconfined by the symmetry. The maximal mixing angles do not correspond to physical mixing, so an Abelian symmetry can, at best, ensure that theta13=0, while leaving the solar and atmospheric mixing angles as free parameters. To generate more features of the best-fit mixing matrix a model with a non-Abelian symmetry and a complicated Higgs sector would have to be used.Comment: 16 pages, no figure

Unification via intermediate symmetry breaking scales with the quartification gauge group

The idea of quark-lepton universality at high energies has been introduced as a natural extension to the standard model. This is achieved by endowing leptons with new degrees of freedom -- leptonic colour, an analogue of the familiar quark colour. Grand and partially unified models which utilise this new gauge symmetry SU(3)_\ell have been proposed in the context of the quartification gauge group SU(3)^4. Phenomenologically successful gauge coupling constant unification without supersymmetry has been demonstrated for cases where the symmetry breaking leaves a residual SU(2)_\ell unbroken. Though attractive, these schemes either incorporate ad hoc discrete symmetries and non-renormalisable mass terms, or achieve only partial unification. We show that grand unified models can be constructed where the quartification group can be broken fully [i.e. no residual SU(2)_\ell] to the standard model gauge group without requiring additional discrete symmetries or higher dimension operators. These models also automatically have suppressed nonzero neutrino masses. We perform a systematic analysis of the renormalisation-group equations for all possible symmetry breaking routes from SU(3)^4 --> SU(3)_q x SU(2)_L x U(1)_Y. This analysis indicates that gauge coupling unification can be achieved for several different symmetry breaking patterns and we outline the requirements that each gives on the unification scale. We also show that the unification scenarios of those models which leave a residual SU(2)_\ell symmetry are not unique. In both symmetry breaking cases, some of the scenarios require new physics at the TeV scale, while others do not allow for new TeV phenomenology in the fermionic sector.Comment: 25 page

Tri-bimaximal mixing, discrete family symmetries, and a conjecture connecting the quark and lepton mixing matrices

Neutrino oscillation experiments (excluding the LSND experiment) suggest a tri-bimaximal form for the lepton mixing matrix. This form indicates that the mixing matrix is probably independent of the lepton masses, and suggests the action of an underlying discrete family symmetry. Using these hints, we conjecture that the contrasting forms of the quark and lepton mixing matrices may both be generated by such a discrete family symmetry. This idea is that the diagonalisation matrices out of which the physical mixing matrices are composed have large mixing angles, which cancel out due to a symmetry when the CKM matrix is computed, but do not do so in the MNS case. However, in the cases where the Higgs bosons are singlets under the symmetry, and the family symmetry commutes with SU(2)L, we prove a no-go theorem: no discrete unbroken family symmetry can produce the required mixing patterns. We then suggest avenues for future research.Comment: 14 pages, no figures, RevTeX4, references adde

Apolipoprotein E and sex modulate fatty acid metabolism in a prospective observational study of cognitive decline

Background: Fatty acids play prominent roles in brain function as they participate in structural, metabolic and signaling processes. The homeostasis of fatty acids and related pathways is known to be impaired in cognitive decline and dementia, but the relationship between these metabolic disturbances and common risk factors, namely the ɛ4 allele of the apolipoprotein E (ApoE-ɛ4) gene and sex, remains elusive. Methods: In order to investigate early alterations associated with cognitive decline in the fatty acid-related serum metabolome, we here applied targeted metabolomics analysis on a nested case-control study (N=368), part of a prospective population cohort on dementia. Results: When considering the entire study population, circulating levels of free fatty acids, acyl-carnitines and pantothenic acid were found to be increased among those participants who had greater odds of cognitive decline over a 12-year follow-up. Interestingly, stratified analyses indicated that these metabolomic alterations were specific for ApoE-ɛ4 non-carriers and women. Conclusions: Altogether, our results highlight that the regulation of fatty acids and related metabolic pathways during ageing and cognitive decline depends on complex inter-relationships between the ApoE-ε4 genotype and sex. A better understanding of the ApoE-ɛ4 and sex dependent modulation of metabolism is essential to elucidate the individual variability in the onset of cognitive decline, which would help develop personalized therapeutic approaches

The TW Hya Disk at 870 microns: Comparison of CO and Dust Radial Structures

We present high resolution (0.3" = 16 AU), high signal-to-noise ratio Submillimeter Array observations of the 870 microns (345 GHz) continuum and CO J=3--2 line emission from the protoplanetary disk around TW Hya. Using continuum and line radiative transfer calculations, those data and the multiwavelength spectral energy distribution are analyzed together in the context of simple two-dimensional parametric disk structure models. Under the assumptions of a radially invariant dust population and (vertically integrated) gas-to-dust mass ratio, we are unable to simultaneously reproduce the CO and dust observations with model structures that employ either a single, distinct outer boundary or a smooth (exponential) taper at large radii. Instead, we find that the distribution of millimeter-sized dust grains in the TW Hya disk has a relatively sharp edge near 60 AU, contrary to the CO emission (and optical/infrared scattered light) that extends to a much larger radius of at least 215 AU. We discuss some possible explanations for the observed radial distribution of millimeter-sized dust grains and the apparent CO-dust size discrepancy, and suggest that they may be hallmarks of substructure in the dust disk or natural signatures of the growth and radial drift of solids that might be expected for disks around older pre-main sequence stars like TW Hya.Comment: ApJ, in press (fixed typo in Equation 4

Epigenetic Effects of Prenatal Stress on 11β-Hydroxysteroid Dehydrogenase-2 in the Placenta and Fetal Brain

Maternal exposure to stress during pregnancy is associated with significant alterations in offspring neurodevelopment and elevated maternal glucocorticoids likely play a central role in mediating these effects. Placental 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2) buffers the impact of maternal glucocorticoid exposure by converting cortisol/corticosterone into inactive metabolites. However, previous studies indicate that maternal adversity during the prenatal period can lead to a down-regulation of this enzyme. In the current study, we examined the impact of prenatal stress (chronic restraint stress during gestational days 14–20) in Long Evans rats on HSD11B2 mRNA in the placenta and fetal brain (E20) and assessed the role of epigenetic mechanisms in these stress-induced effects. In the placenta, prenatal stress was associated with a significant decrease in HSD11B2 mRNA, increased mRNA levels of the DNA methyltransferase DNMT3a, and increased DNA methylation at specific CpG sites within the HSD11B2 gene promoter. Within the fetal hypothalamus, though we find no stress-induced effects on HSD11B2 mRNA levels, prenatal stress induced decreased CpG methylation within the HSD11B2 promoter and increased methylation at sites within exon 1. Within the fetal cortex, HSD11B2 mRNA and DNA methylation levels were not altered by prenatal stress, though we did find stress-induced elevations in DNMT1 mRNA in this brain region. Within individuals, we identified CpG sites within the HSD11B2 gene promoter and exon 1 at which DNA methylation levels were highly correlated between the placenta and fetal cortex. Overall, our findings implicate DNA methylation as a mechanism by which prenatal stress alters HSD11B2 gene expression. These findings highlight the tissue specificity of epigenetic effects, but also raise the intriguing possibility of using the epigenetic status of placenta to predict corresponding changes in the brain

An evaluation of classification systems for stillbirth

<p>Abstract</p> <p>Background</p> <p>Audit and classification of stillbirths is an essential part of clinical practice and a crucial step towards stillbirth prevention. Due to the limitations of the ICD system and lack of an international approach to an acceptable solution, numerous disparate classification systems have emerged. We assessed the performance of six contemporary systems to inform the development of an internationally accepted approach.</p> <p>Methods</p> <p>We evaluated the following systems: Amended Aberdeen, Extended Wigglesworth; PSANZ-PDC, ReCoDe, Tulip and CODAC. Nine teams from 7 countries applied the classification systems to cohorts of stillbirths from their regions using 857 stillbirth cases. The main outcome measures were: the ability to retain the important information about the death using the <it>InfoKeep </it>rating; the ease of use according to the <it>Ease </it>rating (both measures used a five-point scale with a score <2 considered unsatisfactory); inter-observer agreement and the proportion of unexplained stillbirths. A randomly selected subset of 100 stillbirths was used to assess inter-observer agreement.</p> <p>Results</p> <p><it>InfoKeep </it>scores were significantly different across the classifications (<it>p </it>≤ 0.01) due to low scores for Wigglesworth and Aberdeen. CODAC received the highest mean (SD) score of 3.40 (0.73) followed by PSANZ-PDC, ReCoDe and Tulip [2.77 (1.00), 2.36 (1.21), 1.92 (1.24) respectively]. Wigglesworth and Aberdeen resulted in a high proportion of unexplained stillbirths and CODAC and Tulip the lowest. While <it>Ease </it>scores were different (<it>p </it>≤ 0.01), all systems received satisfactory scores; CODAC received the highest score. Aberdeen and Wigglesworth showed poor agreement with kappas of 0.35 and 0.25 respectively. Tulip performed best with a kappa of 0.74. The remainder had good to fair agreement.</p> <p>Conclusion</p> <p>The Extended Wigglesworth and Amended Aberdeen systems cannot be recommended for classification of stillbirths. Overall, CODAC performed best with PSANZ-PDC and ReCoDe performing well. Tulip was shown to have the best agreement and a low proportion of unexplained stillbirths. The virtues of these systems need to be considered in the development of an international solution to classification of stillbirths. Further studies are required on the performance of classification systems in the context of developing countries. Suboptimal agreement highlights the importance of instituting measures to ensure consistency for any classification system.</p

The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention