Novel truncating mutations in CTNND1 cause a dominant craniofacial and cardiac syndrome.

CTNND1 encodes the p120-catenin (p120) protein, which has a wide range of functions, including the maintenance of cell-cell junctions, regulation of the epithelial-mesenchymal transition and transcriptional signalling. Due to advances in next-generation sequencing, CTNND1 has been implicated in human diseases including cleft palate and blepharocheilodontic (BCD) syndrome albeit only recently. In this study, we identify eight novel protein-truncating variants, six de novo, in 13 participants from nine families presenting with craniofacial dysmorphisms including cleft palate and hypodontia, as well as congenital cardiac anomalies, limb dysmorphologies and neurodevelopmental disorders. Using conditional deletions in mice as well as CRISPR/Cas9 approaches to target CTNND1 in Xenopus, we identified a subset of phenotypes that can be linked to p120-catenin in epithelial integrity and turnover, and additional phenotypes that suggest mesenchymal roles of CTNND1. We propose that CTNND1 variants have a wider developmental role than previously described and that variations in this gene underlie not only cleft palate and BCD but may be expanded to a broader velocardiofacial-like syndrome

Analysis of techni-dilaton as a dark matter candidate

The almost conformal dynamics of walking technicolor (TC) implies the existence of the approximate scale invariance, which breaks down spontaneously by the condensation of anti-techni and techni-fermions. According to the Goldstone theorem, a spinless, parity-even particle, called techni-dilaton (TD), then emerges at low energy. If TC exhibits an extreme walking, TD mass is parametrically much smaller than that of techni-fermions (around 1 TeV), while its decay constant is comparable to the cutoff scale of walking TC. We analyze the light, decoupled TD as a dark matter candidate and study cosmological productions of TD, both thermal and non-thermal, in the early Universe. The thermal population is governed dominantly by single TD production processes involving vertices breaking the scale symmetry, while the non-thermal population is by the vacuum misalignment and is accumulated via harmonic and coherent oscillations of misaligned classical TD fields. The non-thermal population turns out to be dominant and large enough to explain the abundance of presently observed dark matter, while the thermal population is highly suppressed due to the large TD decay constant. Several cosmological and astrophysical limits on the light, decoupled TD are examined to find that the TD mass is constrained to be in a range between 0.01 eV and 500 eV. From the combined constraints on cosmological productions and astrophysical observations, we find that the light, decoupled TD can be a good dark matter candidate with the mass around a few hundreds of eV for typical models of (extreme) walking TC. We finally mention possible designated experiments to detect the TD dark matter.Comment: 26 pages. 16 figures; v2, expanded Section 2.4 on composite Higgs in light of newly discovered Higgs-like particle at LH

Cor, a novel carbon monoxide resistance gene, is essential for Mycobacterium tuberculosis pathogenesis

Tuberculosis, caused by Mycobacterium tuberculosis, remains a devastating human infectious disease, causing two million deaths annually. We previously demonstrated that M. tuberculosis induces an enzyme, heme oxygenase (HO1), that produces carbon monoxid

The use of high-resolution (1)H nuclear magnetic resonance (NMR) spectroscopy in the clinical diagnosis of Acanthamoeba

Acanthamoeba are opportunistic protozoan pathogens that can produce sight-threatening keratitis and fatal granulomatous encephalitis. The successful prognosis requires early diagnosis and differentiation of pathogenic Acanthamoeba spp. followed by aggressive treatment regimen. In this study, we tested the use of high-resolution (1)H NMR spectroscopy in the clinical diagnosis of Acanthamoeba. Using NMR spectroscopy combined with Pattern Recognition Analysis (PRA), we analysed variations in the biochemical 'fingerprint' of invasive and non-invasive Acanthamoeba, its closely related genus, Balamuthia mandrillaris, neuropathogenic Escherichia coli K1 strain E44, a laboratory strain of E. coli K-12, HB101, mammalian cells including human brain microvascular endothelial cells and monkey kidney cells. The findings revealed significant variations in the metabolites of amoebae, mammalian cells and bacteria. Interestingly, (1)H NMR spectra provided distinct biochemical profiles of clinical and non-clinical Acanthamoeba isolates highlighting the potential of (1)H NMR spectroscopy combined with PRA for the development of a novel diagnostic test that could rapidly identify pathogenic Acanthamoeba isolates with high sensitivity and specificity