17 research outputs found
Identification of regions critical for the integrity of the TSC1-TSC2-TBC1D7 complex
The TSC1-TSC2-TBC1D7 complex is an important negative regulator of the mechanistic target of rapamycin complex 1 that controls cell growth in response to environmental cues. Inactivating TSC1 and TSC2 mutations cause tuberous sclerosis complex (TSC), an autosomal dominant disorder characterised by the occurrence of benign tumours in various organs and tissues, notably the brain, skin and kidneys. TBC1D7 mutations have not been reported in TSC patients but homozygous inactivation of TBC1D7 causes megaencephaly and intellectual disability. Here, using an exon-specific deletion strategy, we demonstrate that some regions of TSC1 are not necessary for the core function of the TSC1-TSC2 complex. Furthermore, we show that the TBC1D7 binding site is encoded by TSC1 exon 22 and identify amino acid residues involved in the TSC1-TBC1D7 interaction
Glenrothes Borehole Geological well completion report
Investigation of the geothermal potential of the UKSIGLEAvailable from British Library Document Supply Centre- DSC:GPB-9818 / BLDSC - British Library Document Supply CentreGBUnited Kingdo
Determination of Cure Dependent Properties for Curing Simulation of Thick-Walled Composites
Traumatic brain injury in pediatric age group; predictors of outcome in Pediatric Intensive Care Unit
Effect of anisotropy of high-density polyethylene on special features of its behaviour on uniaxial elongation
Targeted Next Generation Sequencing reveals previously unidentified and mutations
Background: Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in and . Conventional DNA diagnostic screens identify a or mutation in 75 - 90% of individuals categorised with definite TSC. The remaining individuals either have a mutation that is undetectable using conventional methods, or possibly a mutation in another as yet unidentified gene. Methods: Here we apply a targeted Next Generation Sequencing (NGS) approach to screen the complete and genomic loci in 7 individuals fulfilling the clinical diagnostic criteria for definite TSC in whom no or mutations were identified using conventional screening methods. Results: We identified and confirmed pathogenic mutations in 3 individuals. In the remaining individuals we identified variants of uncertain clinical significance. The identified variants included mosaic changes, changes located deep in intronic sequences and changes affecting promoter regions that would not have been identified using exon-only based analyses. Conclusions: Targeted NGS of the and loci is a suitable method to increas
Patterns of morphological variability in reintroduced populations with two beaver subspecies Castor fiber orientoeuropaeus and Castor fiber belorussicus (Castoridae, Rodentia) as an example
Long-Acting Gonadotropin-Releasing Hormone Analogue Treatment for Central Precocious Puberty in Maternal Uniparental Disomy Chromosome 14
The Virtual Ventricular Wall: A Tool for Exploring Cardiac Propagation and Arrhythmogenesis
Methods for the experimental and clinical investigation of cardiac arrhythmias are limited to inferring propagation within the myocardium, from surface measurements, or from electrodes at a few sites within the cardiac wall. Biophysically and anatomically detailed computational models of cardiac tissues offer a powerful way for studying the electrical propagation processes and arrhythmias within the virtual heart. We use virtual tissues to study and visualise the effects of patho- and physiological conditions, and pharmacological interventions on transmural propagation in the virtual ventricular walls. Class III drug actions are quantitatively explained by changes induced in the transmural dispersion of action potential duration. We illustrate the automated construction of a virtual anisotropic ventricle from Diffusion Tensor MRI for individual hearts, and use it to explore mechanisms leading to ventricular fibrillation. The virtual ventricular wall provides an effective tool for exploring, evaluating and visualising processes during the initiation and maintenance of ventricular arrhythmias