General anaesthesia with and without intubation for patients with Cornelia de Lange syndrome

We present the use of different methods of general anaesthesia in two patients with Cornelia de Lange syndrome and its contribution to the patients’ oral health.Case 1: The patient was a 22-year-old woman with Cornelia de Lange syndrome who underwent dental treatment under general anaesthesia. She exhibited the physical characteristics of Cornelia de Lange syndrome, including a small mouth, thin lips, short limbs, stiffness of joints and intellectual disability. General anaesthesia without intubation was performed safely eight times. No other complications except hypersensitivity to hypnotic agents were observed.Case 2: The patient was a 10-year-old boy with Cornelia de Lange syndrome who underwent dental treatment under general anaesthesia. He had a history and symptoms of obstructive airway disorders in addition to showing physical characteristics of the syndrome similar to those seen in Case 1. General anaesthesia with nasal intubation was performed safely twice. Computed tomography (CT) of his head and neck produced unremarkable results. These cases demonstrate that both general anaesthesia with and without nasal intubation can be safely used in managing individuals with Cornelia de Lange syndrome during dental treatment.Keywords: general anaesthesia; Cornelia de Lange syndrome; dental treatmen

Signature of short distance physics on inflation power spectrum and CMB anisotropy

The inflaton field responsible for inflation may not be a canonical fundamental scalar. It is possible that the inflaton is a composite of fermions or it may have a decay width. In these cases the standard procedure for calculating the power spectrum is not applicable and a new formalism needs to be developed to determine the effect of short range interactions of the inflaton on the power spectrum and the CMB anisotropy. We develop a general formalism for computing the power spectrum of curvature perturbations for such non-canonical cases by using the flat space K\"all\'en-Lehmann spectral function in curved quasi-de Sitter space assuming implicitly that the Bunch-Davis boundary conditions enforces the inflaton mode functions to be plane wave in the short wavelength limit and a complete set of mode functions exists in quasi-de Sitter space. It is observed that the inflaton with a decay width suppresses the power at large scale while a composite inflaton's power spectrum oscillates at large scales. These observations may be vindicated in the WMAP data and confirmed by future observations with PLANCK.Comment: 17 pages, 4 figures, Extended journal version, Accepted for publication in JCA

Reconstruction of the Primordial Power Spectrum by Direct Inversion

We introduce a new method for reconstructing the primordial power spectrum, $P(k)$, directly from observations of the Cosmic Microwave Background (CMB). We employ Singular Value Decomposition (SVD) to invert the radiation perturbation transfer function. The degeneracy of the multipole $\ell$ to wavenumber $k$ linear mapping is thus reduced. This enables the inversion to be carried out at each point along a Monte Carlo Markov Chain (MCMC) exploration of the combined $P(k)$ and cosmological parameter space. We present best--fit $P(k)$ obtained with this method along with other cosmological parameters.Comment: 23 pages, 9 figure

The lncRNA HOTAIR transcription is controlled by HNF4α-induced chromatin topology modulation

The expression of the long noncoding RNA HOTAIR (HOX Transcript Antisense Intergenic RNA) is largely deregulated in epithelial cancers and positively correlates with poor prognosis and progression of hepatocellular carcinoma and gastrointestinal cancers. Furthermore, functional studies revealed a pivotal role for HOTAIR in the epithelial-to-mesenchymal transition, as this RNA is causal for the repressive activity of the master factor SNAIL on epithelial genes. Despite the proven oncogenic role of HOTAIR, its transcriptional regulation is still poorly understood. Here hepatocyte nuclear factor 4-α (HNF4α), as inducer of epithelial differentiation, was demonstrated to directly repress HOTAIR transcription in the mesenchymal-to epithelial transition. Mechanistically, HNF4α was found to cause the release of a chromatin loop on HOTAIR regulatory elements thus exerting an enhancer-blocking activity

The Snail repressor recruits EZH2 to specific genomic sites through the enrollment of the lncRNA HOTAIR in epithelial-to-mesenchymal transition

The transcription factor Snail is a master regulator of cellular identity and epithelial-to-mesenchymal transition (EMT) directly repressing a broad repertoire of epithelial genes. How chromatin modifiers instrumental to its activity are recruited to Snail-specific binding sites is unclear. Here we report that the long non-coding RNA (lncRNA) HOTAIR (for HOX Transcript Antisense Intergenic RNA) mediates a physical interaction between Snail and enhancer of zeste homolog 2 (EZH2), an enzymatic subunit of the polycomb-repressive complex 2 and the main writer of chromatin-repressive marks. The Snail-repressive activity, here monitored on genes with a pivotal function in epithelial and hepatic morphogenesis, differentiation and cell-type identity, depends on the formation of a tripartite Snail/HOTAIR/EZH2 complex. These results demonstrate an lncRNA-mediated mechanism by which a transcriptional factor conveys a general chromatin modifier to specific genes, thereby allowing the execution of hepatocyte transdifferentiation; moreover, they highlight HOTAIR as a crucial player in the Snail-mediated EMT.Oncogene advance online publication, 25 July 2016; doi:10.1038/onc.2016.260

Signatures of heavy Majorana neutrinos and HERA's isolated lepton events

The graph of neutrinoless double beta decay is applied to HERA and generalized to final states with any two charged leptons. Considered is the case in which one of the two escapes typical identification criteria and the case when a produced tau decays hadronically. Both possibilities give one isolated lepton with high transverse momentum, hadronic activity and an imbalance in transverse momentum. We examine the kinematical properties of these events and compare them with the high p_T isolated leptons reported by the H1 collaboration. Their positive charged muon events can be explained by the ``double beta'' process and we discuss possibilities for the precise determination which original final state produced the single isolated lepton. To confirm our hypothesis one should search in the data for high pseudorapidity and/or low p_T leptons or for additional separated jets.Comment: 19 pages with 14 figures, minor change

Adenomatous Polyposis Coli Regulates Axon Arborization and Cytoskeleton Organization via Its N-Terminus

Conditional deletion of APC leads to marked disruption of cortical development and to excessive axonal branching of cortical neurons. However, little is known about the cell biological basis of this neuronal morphological regulation. Here we show that APC deficient cortical neuronal growth cones exhibit marked disruption of both microtubule and actin cytoskeleton. Functional analysis of the different APC domains revealed that axonal branches do not result from stabilized β-catenin, and that the C-terminus of APC containing microtubule regulatory domains only partially rescues the branching phenotype. Surprisingly, the N-terminus of APC containing the oligomerization domain and the armadillo repeats completely rescues the branching and cytoskeletal abnormalities. Our data indicate that APC is required for appropriate axon morphological development and that the N-terminus of APC is important for regulation of the neuronal cytoskeleton

KSHV PAN RNA Associates with Demethylases UTX and JMJD3 to Activate Lytic Replication through a Physical Interaction with the Virus Genome

Kaposi's sarcoma-associated herpesvirus (KSHV) is the cause of Kaposi's sarcoma and body cavity lymphomas. KSHV lytic infection produces PAN RNA, a highly abundant noncoding polyadenylated transcript that is retained in the nucleus. We recently demonstrated that PAN RNA interacts with several viral and cellular factors and can disregulate the expression of genes that modulate immune response. In an effort to define the role of PAN RNA in the context of the virus genome we generated a recombinant BACmid that deleted the PAN RNA locus. Because of the apparent duplication of the PAN RNA locus in BAC36, we generated BAC36CR, a recombinant BACmid that removes the duplicated region. BAC36CR was used as a template to delete most of the PAN RNA locus to generate BAC36CRΔPAN. BAC36CRΔPAN failed to produce supernatant virus and displayed a general decrease in mRNA accumulation of representative immediate early, early and late genes. Most strikingly, K-Rta expression was decreased in lytically induced BAC36CRΔPAN-containing cell lines at early and late time points post induction. Expression of PAN RNA in trans in BAC36CRΔPAN containing cells resulted in an increase in K-Rta expression, however K-Rta over expression failed to rescue BAC36CRΔPAN, suggesting that PAN RNA plays a wider role in virus replication. To investigate the role of PAN RNA in the activation of K-Rta expression, we demonstrate that PAN RNA physically interacts with the ORF50 promoter. RNA chromatin immunoprecipitation assays show that PAN RNA interacts with demethylases JMJD3 and UTX, and the histone methyltransferase MLL2. Consistent with the interaction with demethylases, expression of PAN RNA results in a decrease of the repressive H3K27me3 mark at the ORF50 promoter. These data support a model where PAN RNA is a multifunctional regulatory transcript that controls KSHV gene expression by mediating the modification of chromatin by targeting the KSHV repressed genome

Reconstruction of the Primordial Power Spectrum using Temperature and Polarisation Data from Multiple Experiments

We develop a method to reconstruct the primordial power spectrum, P(k), using both temperature and polarisation data from the joint analysis of a number of Cosmic Microwave Background (CMB) observations. The method is an extension of the Richardson-Lucy algorithm, first applied in this context by Shafieloo & Souradeep. We show how the inclusion of polarisation measurements can decrease the uncertainty in the reconstructed power spectrum. In particular, the polarisation data can constrain oscillations in the spectrum more effectively than total intensity only measurements. We apply the estimator to a compilation of current CMB results. The reconstructed spectrum is consistent with the best-fit power spectrum although we find evidence for a `dip' in the power on scales k ~ 0.002 Mpc^-1. This feature appears to be associated with the WMAP power in the region 18 < l < 26 which is consistently below best--fit models. We also forecast the reconstruction for a simulated, Planck-like survey including sample variance limited polarisation data.Comment: 8 pages, 5 figures, comments welcom