13 research outputs found

    Using brain cell-type-specific protein interactomes to interpret neurodevelopmental genetic signals in schizophrenia

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    Genetics have nominated many schizophrenia risk genes and identified convergent signals between schizophrenia and neurodevelopmental disorders. However, functional interpretation of the nominated genes in the relevant brain cell types is often lacking. We executed interaction proteomics for six schizophrenia risk genes that have also been implicated in neurodevelopment in human induced cortical neurons. The resulting protein network is enriched for common variant risk of schizophrenia in Europeans and East Asians, is down-regulated in layer 5/6 cortical neurons of individuals affected by schizophrenia, and can complement fine-mapping and eQTL data to prioritize additional genes in GWAS loci. A sub-network centered on HCN1 is enriched for common variant risk and contains proteins (HCN4 and AKAP11) enriched for rare protein-truncating mutations in individuals with schizophrenia and bipolar disorder. Our findings showcase brain cell-type-specific interactomes as an organizing framework to facilitate interpretation of genetic and transcriptomic data in schizophrenia and its related disorders

    Hemangioblastoma of filum terminale associated with arteriovenous shunting

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    Background: Spinal arteriovenous shunt typically presents in middle age or in the elderly with a strong male predilection. The clinical presentation is usually progressive neurological deficits such as paraparesis or incontinence due to cord edema, although back pain is also a common presentation. Progress of neurological deficit is typically stopped by occlusion of the shunt (surgically or endovascularly), but the return of loss of function may be found in less than half of these patients. In contrast, spinal hemangioblastomas usually occur in adults, and the most common presentation is pain with radiculopathy. Location in the filum terminale is very rare. Case Description: After a review of the medical literature, we identified 7 cases of hemangioblastomas arising from the filum terminale (Am J Neuroradiol. 2005;26:936-945; Acta Neurochir [Wien]. 2000;142:1059-1062; J Neurosurg Sci. 2001;45:58-62; J Clin Neurosci. 2006;13:285-288; Neurosurgery. 1999;44:220-223; Clin Neurol Neurosurg. 1985;87:55-59).We report an additional case of a filum terminale hemangioblastoma occurring in a 64-year-old man with 1 month exacerbation of chronic low back pain. Preoperatively, it was misdiagnosed as filum terminale arteriovenous fistula. Conclusion: Even with modern imaging, preoperative diagnosis can still be difficult. © 2007 Elsevier Inc. All rights reserved.link_to_subscribed_fulltex

    Cell wall swelling, fracture mode, and the mechanical properties of cherry fruit skins are closely related

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    Main conclusion: Cell wall swelling, fracture mode (along the middle lamellae vs. across cell walls), stiffness, and pressure at fracture of the sweet cherry fruit skin are closely related. Skin cracking is a common phenomenon in many crops bearing fleshy fruit. The objectives were to investigate relationships between the mode of fracture, the extent of cell wall swelling, and the mechanical properties of the fruit skin using sweet cherry (Prunus avium) as a model. Cracking was induced by incubating whole fruit in deionised water or by fracturing exocarp segments (ESs) in biaxial tensile tests. The fracture mode of epidermal cells was investigated by light microscopy. In biaxial tensile tests, the anticlinal cell walls of the ES fractured predominantly across the cell walls (rather than along) and showed no cell wall swelling. In contrast, fruit incubated in water fractured predominantly along the anticlinal epidermal cell walls and the cell walls were swollen. Swelling of cell walls also occurred when ESs were incubated in malic acid, in hypertonic solutions of sucrose, or in water. Compared to the untreated controls, these treatments resulted in more frequent fractures along the cell walls, lower pressures at fracture (pfracture), and lower moduli of elasticity (E, i.e., less stiff). Conversely, compared to the untreated controls, incubating the ES in CaCl2 and in high concentrations of ethanol resulted in thinner cell walls, in less frequent fractures along the cell walls, higher E and pfracture. Our study demonstrates that fracture mode, stiffness, and pressure at fracture are closely related to cell wall swelling. A number of other factors, including cultivar, ripening stage, turgor, CaCl2, and malic acid, exert their effects only indirectly, i.e., by affecting cell wall swelling. The final publication is available at Springer via http://dx.doi.org/10.1007/s00425-016-2639-7DF

    Molecular Biology of Inhibitory Amino Acid Receptors

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