566 research outputs found
Bi-allelic CAMSAP1 variants cause a clinically recognizable neuronal migration disorder
Non-centrosomal microtubules are essential cytoskeletal filaments that are important for neurite formation, axonal transport, and neuronal migration. They require stabilization by microtubule minus-end-targeting proteins including the CAMSAP family of molecules. Using exome sequencing on samples from five unrelated families, we show that bi-allelic CAMSAP1 loss-of-function variants cause a clinically recognizable, syndromic neuronal migration disorder. The cardinal clinical features of the syndrome include a characteristic craniofacial appearance, primary microcephaly, severe neurodevelopmental delay, cortical visual impairment, and seizures. The neuroradiological phenotype comprises a highly recognizable combination of classic lissencephaly with a posterior more severe than anterior gradient similar to PAFAH1B1(LIS1)-related lissencephaly and severe hypoplasia or absence of the corpus callosum; dysplasia of the basal ganglia, hippocampus, and midbrain; and cerebellar hypodysplasia, similar to the tubulinopathies, a group of monogenic tubulin-associated disorders of cortical dysgenesis. Neural cell rosette lineages derived from affected individuals displayed findings consistent with these phenotypes, including abnormal morphology, decreased cell proliferation, and neuronal differentiation. Camsap1-null mice displayed increased perinatal mortality, and RNAScope studies identified high expression levels in the brain throughout neurogenesis and in facial structures, consistent with the mouse and human neurodevelopmental and craniofacial phenotypes. Together our findings confirm a fundamental role of CAMSAP1 in neuronal migration and brain development and define bi-allelic variants as a cause of a clinically distinct neurodevelopmental disorder in humans and mice
Feasibility of comparing medical management and surgery (with neurosurgery or stereotactic radiosurgery) with medical management alone in people with symptomatic brain cavernoma - protocol for the Cavernomas:A Randomised Effectiveness (CARE) pilot trial
Ultrabroadband Polarization Insensitive Hybrid using Multiplane Light Conversion
We designed, fabricated and tested an optical hybrid that supports an octave
of bandwidth (900-1800 nm) and below 4-dB insertion loss using multiplane light
conversion. Measured phase errors are below 3-degree across a measurement
bandwidth of 390 nm.Comment: 3 pages, 4 figures, accepted by OFC 202
Secreted CLIC3 drives cancer progression through its glutathione-dependent oxidoreductase activity
The secretome of cancer and stromal cells generates a microenvironment that contributes to tumour cell invasion and angiogenesis. Here we compare the secretome of human mammary normal and cancer-associated fibroblasts (CAFs). We discover that the chloride intracellular channel protein 3 (CLIC3) is an abundant component of the CAF secretome. Secreted CLIC3 promotes invasive behaviour of endothelial cells to drive angiogenesis and increases invasiveness of cancer cells both in vivo and in 3D cell culture models, and this requires active transglutaminase-2 (TGM2). CLIC3 acts as a glutathione-dependent oxidoreductase that reduces TGM2 and regulates TGM2 binding to its cofactors. Finally, CLIC3 is also secreted by cancer cells, is abundant in the stromal and tumour compartments of aggressive ovarian cancers and its levels correlate with poor clinical outcome. This work reveals a previously undescribed invasive mechanism whereby the secretion of a glutathione-dependent oxidoreductase drives angiogenesis and cancer progression by promoting TGM2-dependent invasion
Medical management and surgery versus medical management alone for symptomatic cerebral cavernous malformation (CARE): a feasibility study and randomised, open, pragmatic, pilot phase trial
Dynamic biospeckle analysis, a new tool for the fast screening of plant nematicide selectivity
Narrowband Biphotons: Generation, Manipulation, and Applications
In this chapter, we review recent advances in generating narrowband biphotons
with long coherence time using spontaneous parametric interaction in monolithic
cavity with cluster effect as well as in cold atoms with electromagnetically
induced transparency. Engineering and manipulating the temporal waveforms of
these long biphotons provide efficient means for controlling light-matter
quantum interaction at the single-photon level. We also review recent
experiments using temporally long biphotons and single photons.Comment: to appear as a book chapter in a compilation "Engineering the
Atom-Photon Interaction" published by Springer in 2015, edited by A.
Predojevic and M. W. Mitchel
Prospect theory and tax evasion: a reconsideration of the Yitzhaki puzzle
The standard expected utility (EUT) model of tax evasion predicts that evasion is decreasing in the marginal tax rate (the Yitzhaki puzzle). Recent literature shows cases in which incorporating prospect theory (PT) does and does not overturn the Puzzle. In a general environment that nests both PT and EUT preferences, we provide a detailed study of how the elements of PT affect the Puzzle. PT does not always reverse the Puzzle, hence we give and interpret conditions for when it does and does not. When allowing for stigma and/or variable audit probability, PT reverses the Puzzle in the same way and with the same limitations as does EUT, if equally augmented
Comparison of dose calculations between pencil-beam and Monte Carlo algorithms of the iPlan RT in arc therapy using a homogenous phantom with 3DVH software
- …