Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The TUBA1A gene encodes tubulin alpha-1A, a protein that is highly expressed in the fetal brain. Alpha- and beta-tubulin subunits form dimers, which then co-assemble into microtubule polymers: dynamic, scaffold-like structures that perform key functions during neurogenesis, neuronal migration, and cortical organisation. Mutations in TUBA1A have been reported to cause a range of brain malformations. We describe four unrelated patients with the same de novo missense mutation in TUBA1A, c.5G>A, p.(Arg2His), as found by next generation sequencing. Detailed comparison revealed similar brain phenotypes with mild variability. Shared features included developmental delay, microcephaly, hypoplasia of the cerebellar vermis, dysplasia or thinning of the corpus callosum, small pons, and dysmorphic basal ganglia. Two of the patients had bilateral perisylvian polymicrogyria. We examined the effects of the p.(Arg2His) mutation by computer-based protein structure modelling and heterologous expression in HEK-293 cells. The results suggest the mutation subtly impairs microtubule function, potentially by affecting inter-dimer interaction. Based on its sequence context, c.5G>A is likely to be a common recurrent mutation. We propose that the subtle functional effects of p.(Arg2His) may allow for other factors (such as genetic background or environmental conditions) to influence phenotypic outcome, thus explaining the mild variability in clinical manifestations.
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PMID:Clinical and Functional Characterization of the Recurrent TUBA1A p.(Arg2His) Mutation. 3008 72

Hydrogel scaffolds are important materials in tissue engineering, and their characterization is essential to determine potential biomedical applications according to their mechanical and structural behavior. In this work, silk fibroin hydrogels were synthesized by two different methods (vortex and sonication), and agarose hydrogels were also obtained for comparison purposes. Samples were characterized by scanning electron microscopy, infrared analysis, thermo-gravimetrical analysis, confined compression test, and rheological test. The results indicate that nanofibers can be obtained via both silk fibroin and agarose hydrogels. The mechanical tests showed that the Young's modulus is similar to those found in the literature, with the highest value for agarose hydrogels. All the hydrogels showed a shear-thinning behavior. Additionally, the MTT test revealed that silk fibroin hydrogels had low cytotoxicity in THP-1 and HEK-293 cells, whereas the agarose hydrogels showed high toxicity for the THP-1 cell line. The results indicate that silk fibroin hydrogels obtained from a Colombian silkworm hybrid are suitable for the development of scaffolds, with potential applications in tissue engineering.
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PMID:Silk fibroin hydrogels from the Colombian silkworm Bombyx mori L: Evaluation of physicochemical properties. 3083 Sep 43

Hybrid interfaces between living cells and nano/microstructured scaffolds have huge application potential in biotechnology, spanning from regenerative medicine and stem cell therapies to localized drug delivery and from biosensing and tissue engineering to neural computing. However, 3D architectures based on semiconducting polymers, endowed with responsivity to visible light, have never been considered. Here, we apply for the first time a push-coating technique to realize high aspect ratio polymeric pillars, based on polythiophene, showing optimal biocompatibility and allowing for the realization of soft, 3D cell cultures of both primary neurons and cell line models. HEK-293 cells cultured on top of polymer pillars display a remarkable change in the cell morphology and a sizable enhancement of the membrane capacitance due to the cell membrane thinning in correspondence to the pillars' top surface, without negatively affecting cell proliferation. Electrophysiology properties and synapse number of primary neurons are also very well preserved. In perspective, high aspect ratio semiconducting polymer pillars may find interesting applications as soft, photoactive elements for cell activity sensing and modulation.
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PMID:High-Aspect-Ratio Semiconducting Polymer Pillars for 3D Cell Cultures. 3135 41