Denominators of Eisenstein cohomology classes for GL_2 over imaginary quadratic fields

We study the arithmetic of Eisenstein cohomology classes (in the sense of G. Harder) for symmetric spaces associated to GL_2 over imaginary quadratic fields. We prove in many cases a lower bound on their denominator in terms of a special L-value of a Hecke character providing evidence for a conjecture of Harder that the denominator is given by this L-value. We also prove under some additional assumptions that the restriction of the classes to the boundary of the Borel-Serre compactification of the spaces is integral. Such classes are interesting for their use in congruences with cuspidal classes to prove connections between the special L-value and the size of the Selmer group of the Hecke character.Comment: 37 pages; strengthened integrality result (Proposition 16), corrected statement of Theorem 3, and revised introductio

Production and Decay of Neutralinos in the Next-To-Minimal Supersymmetric Standard Model

Within the framework of the Next-To-Minimal Supersymmetric Standard Model (NMSSM) we study neutralino production $e^+e^- \longrightarrow \tilde{\chi}^0_i \tilde{\chi}^0_j$ ($i,j=1,\ldots ,5$) at center-of-mass energies between 100 and 600 GeV and the decays of the heavier neutralinos into the LSP plus a fermion pair, a photon or a Higgs boson. For representative gaugino/higgsino mixing scenarios, where the light neutralinos have significant singlet components, we find some striking differences between the NMSSM and the minimal supersymmetric model. Since in the NMSSM neutralino and Higgs sector are strongly correlated, the decay of the second lightest neutralino into a Higgs boson and the LSP often is kinematically possible and even dominant in a large parameter region of typical NMSSM scenarios. Also, the decay rates into final states with a photon may be enhanced.Comment: 36 pages, latex, 10 uuendcoded figures, complete ps file available at ftp://ftp.physik.uni-wuerzburg.de/pub/preprint/WUE-ITP-95-021.ps.g

Position effects at the FGF8 locus are associated with femoral hypoplasia

Copy-number variations (CNVs) are a common cause of congenital limb malformations and are interpreted primarily on the basis of their effect on gene dosage. However, recent studies show that CNVs also influence the 3D genome chromatin organization. The functional interpretation of whether a phenotype is the result of gene dosage or a regulatory position effect remains challenging. Here, we report on two unrelated families with individuals affected by bilateral hypoplasia of the femoral bones, both harboring de novo duplications on chromosome 10q24.32. The ∼0.5 Mb duplications include FGF8, a key regulator of limb development and several limb enhancer elements. To functionally characterize these variants, we analyzed the local chromatin architecture in the affected individuals’ cells and re-engineered the duplications in mice by using CRISPR-Cas9 genome editing. We found that the duplications were associated with ectopic chromatin contacts and increased FGF8 expression. Transgenic mice carrying the heterozygous tandem duplication including Fgf8 exhibited proximal shortening of the limbs, resembling the human phenotype. To evaluate whether the phenotype was a result of gene dosage, we generated another transgenic mice line, carrying the duplication on one allele and a concurrent Fgf8 deletion on the other allele, as a control. Surprisingly, the same malformations were observed. Capture Hi-C experiments revealed ectopic interaction with the duplicated region and Fgf8, indicating a position effect. In summary, we show that duplications at the FGF8 locus are associated with femoral hypoplasia and that the phenotype is most likely the result of position effects altering FGF8 expression rather than gene dosage effects.M.S. and A.S.-S. were supported by the Polish National Science Centre (UMO-2016/23/N/NZ2/02362 to M.S. and UMO-2016/21/D/NZ5/00064 to A.S.-S.). A.S.-S. was also supported by the Polish National Science Centre scholarship for PhD students (UMO-2013/08/T/NZ2/00027). C.L. is supported by postdoctoral Beatriu de Pinós from Secretaria d’Universitats I Recerca del Departament d’Empresa i Coneixement de la Generalitat de Catalunya and by the Marie Sklodowska-Curie COFUND program from H2020 (2018-BP-00055). A.J. was supported by the Polish National Science Centre (UMO-2016/22/E/NZ5/00270) as well as the Polish National Centre for Research and Development (LIDER/008/431/L-4/12/NCBR/2013). M.S. is supported by grants from the Deutsche Forschungsgemeinschaft (DFG) (SP1532/3-1, SP1532/4-1, and SP1532/5-1), the Max Planck Foundation, and the Deutsches Zentrum für Luft- und Raumfahrt (DLR 01GM1925)

Difficult Scenarios for NMSSM Higgs Discovery at the LHC

We identify scenarios not ruled out by LEP data in which NMSSM Higgs detection at the LHC will be particularly challenging. We first review the `no-lose' theorem for Higgs discovery at the LHC that applies if Higgs bosons do not decay to other Higgs bosons - namely, with L=300 fb^-1, there is always one or more `standard' Higgs detection channel with at least a 5 sigma signal. However, we provide examples of no-Higgs-to-Higgs cases for which all the standard signals are no larger than 7 sigma implying that if the available L is smaller or the simulations performed by ATLAS and CMS turn out to be overly optimistic, all standard Higgs signals could fall below 5 sigma even in the no-Higgs-to-Higgs part of NMSSM parameter space. In the vast bulk of NMSSM parameter space, there will be Higgs-to-Higgs decays. We show that when such decays are present it is possible for all the standard detection channels to have very small significance. In most such cases, the only strongly produced Higgs boson is one with fairly SM-like couplings that decays to two lighter Higgs bosons (either a pair of the lightest CP-even Higgs bosons, or, in the largest part of parameter space, a pair of the lightest CP-odd Higgs bosons). A number of representative bench-mark scenarios of this type are delineated in detail and implications for Higgs discovery at various colliders are discussed.Comment: 31 pages, 5 figure

Charged Higgs bosons in the Next-to MSSM (NMSSM)

The charged Higgs boson decays $H^\pm\to W^\pm A_1$ and $H^\pm\to W^\pm h_i$ are studied in the framework of the next-to Minimal Supersymmetric Standard Model (NMSSM). It is found that the decay rate for $H^\pm\to W^\pm A_1$ can exceed the rates for the $\tau^\pm\nu$ and $tb$ channels both below and above the top-bottom threshold. The dominance of $H^\pm\to W^\pm A_1$ is most readily achieved when $A_1$ has a large doublet component and small mass. We also study the production process $pp\to H^\pm A_1$ at the LHC followed by the decay $H^\pm\to W^\pm A_1$ which leads to the signature $W^\pm A_1 A_1$. We suggest that $p p\to H^\pm A_1$ is a promising discovery channel for a light charged Higgs boson in the NMSSM with small or moderate $\tan\beta$ and dominant decay mode $H^\pm \to W^\pm A_1$. This $W^\pm A_1 A_1$ signature can also arise from the Higgsstrahlung process $pp\to W^\pm h_1$ followed by the decay $h_1\to A_1 A_1$. It is shown that there exist regions of parameter space where these processes can have comparable cross sections and we suggest that their respective signals can be distinguished at the LHC by using appropriate reconstruction methods.Comment: 20 pages, 22 eps figures, more reference adde

Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling

Objective: Our previous coeliac disease genome-wide association study (GWAS) implicated risk variants in the human leucocyte antigen (HLA) region and eight novel risk regions. To identify more coeliac disease loci, we selected 458 single nucleotide polymorphisms (SNPs) that showed more modest association in the GWAS for genotyping and analysis in four independent cohorts. Design: 458 SNPs were assayed in 1682 cases and 3258 controls from three populations (UK, Irish and Dutch). We combined the results with the original GWAS cohort (767 UK cases and 1422 controls); six SNPs showed association with p Results: We identified two novel coeliac disease risk regions: 6q23.3 (OLIG3-TNFAIP3) and 2p16.1 (REL), both of which reached genome-wide significance in the combined analysis of all 2987 cases and 5273 controls (rs2327832 p= 1.3x10(-08), and rs842647 p= 5.26x10(-07)). We investigated the expression of these genes in the RNA isolated from biopsies and from whole blood RNA. We did not observe any changes in gene expression, nor in the correlation of genotype with gene expression. Conclusions: Both TNFAIP3 (A20, at the protein level) and REL are key mediators in the nuclear factor kappa B (NF-kappa B) inflammatory signalling pathway. For the first time, a role for primary heritable variation in this important biological pathway predisposing to coeliac disease has been identified. Currently, the HLA risk factors and the 10 established non-HLA risk factors explain similar to 40% of the heritability of coeliac disease

A suberized exodermis is required for tomato drought tolerance.

Plant roots integrate environmental signals with development using exquisite spatiotemporal control. This is apparent in the deposition of suberin, an apoplastic diffusion barrier, which regulates flow of water, solutes and gases, and is environmentally plastic. Suberin is considered a hallmark of endodermal differentiation but is absent in the tomato endodermis. Instead, suberin is present in the exodermis, a cell type that is absent in the model organism Arabidopsis thaliana. Here we demonstrate that the suberin regulatory network has the same parts driving suberin production in the tomato exodermis and the Arabidopsis endodermis. Despite this co-option of network components, the network has undergone rewiring to drive distinct spatial expression and with distinct contributions of specific genes. Functional genetic analyses of the tomato MYB92 transcription factor and ASFT enzyme demonstrate the importance of exodermal suberin for a plant water-deficit response and that the exodermal barrier serves an equivalent function to that of the endodermis and can act in its place

Informal and formal reconciliation strategies of older peoples’ working carers: the European carers@work project

Faced with a historically unprecedented process of demographic ageing, many European societies implemented pension reforms in recent years to extend working lives. Although aimed at rebalancing public pension systems, this approach has the unintended side effect that it also extends the number of years in which working carers have to juggle the conflicting demands of employment and caregiving. This not only impinges on working carers’ well-being and ability to continue providing care but also affects European enterprises’ capacity to generate growth which increasingly relies on ageing workforces. The focus of this paper will thus be a cross-national comparison of individual reconciliation strategies and workplace-related company policies aimed at enabling working carers to reconcile both conflicting roles in four different European welfare states: Germany, Italy, Poland, and the United Kingdom

The genetic architecture of the human cerebral cortex

INTRODUCTION The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure. RATIONALE To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 individuals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations. RESULTS We identified 306 nominally genome-wide significant loci (P < 5 × 10−8) associated with cortical structure in a discovery sample of 33,992 participants of European ancestry. Of the 299 loci for which replication data were available, 241 loci influencing surface area and 14 influencing thickness remained significant after replication, with 199 loci passing multiple testing correction (P < 8.3 × 10−10; 187 influencing surface area and 12 influencing thickness). Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness; surface area and thickness showed a negative genetic correlation (rG = −0.32, SE = 0.05, P = 6.5 × 10−12), which suggests that genetic influences have opposing effects on surface area and thickness. Bioinformatic analyses showed that total surface area is influenced by genetic variants that alter gene regulatory activity in neural progenitor cells during fetal development. By contrast, average thickness is influenced by active regulatory elements in adult brain samples, which may reflect processes that occur after mid-fetal development, such as myelination, branching, or pruning. When considered together, these results support the radial unit hypothesis that different developmental mechanisms promote surface area expansion and increases in thickness. To identify specific genetic influences on individual cortical regions, we controlled for global measures (total surface area or average thickness) in the regional analyses. After multiple testing correction, we identified 175 loci that influence regional surface area and 10 that influence regional thickness. Loci that affect regional surface area cluster near genes involved in the Wnt signaling pathway, which is known to influence areal identity. We observed significant positive genetic correlations and evidence of bidirectional causation of total surface area with both general cognitive functioning and educational attainment. We found additional positive genetic correlations between total surface area and Parkinson’s disease but did not find evidence of causation. Negative genetic correlations were evident between total surface area and insomnia, attention deficit hyperactivity disorder, depressive symptoms, major depressive disorder, and neuroticism. CONCLUSION This large-scale collaborative work enhances our understanding of the genetic architecture of the human cerebral cortex and its regional patterning. The highly polygenic architecture of the cortex suggests that distinct genes are involved in the development of specific cortical areas. Moreover, we find evidence that brain structure is a key phenotype along the causal pathway that leads from genetic variation to differences in general cognitive function