Failure of Fluid Absorption in the Endolymphatic Sac Initiates Cochlear Enlargement that Leads to Deafness in Mice Lacking Pendrin Expression

Mutations of SLC26A4 are among the most prevalent causes of hereditary deafness. Deafness in the corresponding mouse model, Slc26a4−/−, results from an abnormally enlarged cochlear lumen. The goal of this study was to determine whether the cochlear enlargement originates with defective cochlear fluid transport or with a malfunction of fluid transport in the connected compartments, which are the vestibular labyrinth and the endolymphatic sac. Embryonic inner ears from Slc26a4+/− and Slc26a4−/− mice were examined by confocal microscopy ex vivo or after 2 days of organ culture. Culture allowed observations of intact, ligated or partially resected inner ears. Cochlear lumen formation was found to begin at the base of the cochlea between embryonic day (E) 13.5 and 14.5. Enlargement was immediately evident in Slc26a4−/− compared to Slc26a4+/− mice. In Slc26a4+/− and Slc26a4−/− mice, separation of the cochlea from the vestibular labyrinth by ligation at E14.5 resulted in a reduced cochlear lumen. Resection of the endolymphatic sacs at E14.5 led to an enlarged cochlear lumen in Slc26a4+/− mice but caused no further enlargement of the already enlarged cochlear lumen in Slc26a4−/− mice. Ligation or resection performed later, at E17.5, did not alter the cochlea lumen. In conclusion, the data suggest that cochlear lumen formation is initiated by fluid secretion in the vestibular labyrinth and temporarily controlled by fluid absorption in the endolymphatic sac. Failure of fluid absorption in the endolymphatic sac due to lack of Slc26a4 expression appears to initiate cochlear enlargement in mice, and possibly humans, lacking functional Slc26a4 expression

Investigation of thermal resistance and power consumption in Ga-doped indium oxide (In2O3) nanowire phase change random access memory

The resistance stability and thermal resistance of phase change memory devices using similar to 40 nm diameter Ga-doped In2O3 nanowires (Ga:In2O3 NW) with different Ga-doping concentrations have been investigated. The estimated resistance stability (R(t)/R-0 ratio) improves with higher Ga concentration and is dependent on annealing temperature. The extracted thermal resistance (R-th) increases with higher Ga-concentration and thus the power consumption can be reduced by similar to 90% for the 11.5% Ga: In2O3 NW, compared to the 2.1% Ga: In2O3 NW. The excellent characteristics of Ga-doped In2O3 nanowire devices offer an avenue to develop low power and reliable phase change random access memory applications. (C) 2014 AIP Publishing LLC.X113sciescopu

Nanomedicine: Interaction of biomimetic apatite colloidal nanoparticles with human blood components

This contribution investigates the interaction of two types of biomimetic-apatite colloidal nanoparticles (negatively-charged 47nm, and positively-charged 190nm NPs) with blood components, namely red blood cells (RBC) and plasma proteins, with the view to inspect their hemocompatibility. The NPs, preliminarily characterized by XRD, FTIR and DLS, showed low hemolysis ratio (typically lower than 5%) illustrating the high compatibility of such NPs with respect to RBC, even at high concentration (up to 10mg/ml). The presence of glucose as water-soluble matrix for freeze-dried and re-dispersed colloids led to slightly increased hemolysis as compared to glucose-free formulations. NPs/plasma protein interaction was then followed, via non-specific protein fluorescence quenching assays, by contact with whole human blood plasma. The amount of plasma proteins in interaction with the NPs was evaluated experimentally, and the data were fitted with the Hill plot and Stern-Volmer models. In all cases, binding constants of the order of 101–102 were found. These values, significantly lower than those reported for other types of nanoparticles or molecular interactions, illustrate the fairly inert character of these colloidal NPs with respect to plasma proteins, which is desirable for circulating injectable suspensions. Results were discussed in relation with particle surface charge and mean particle hydrodynamic diameter (HD). On the basis of these hemocompatibility data, this study significantly complements previous results relative to the development and nontoxicity of biomimetic-apatite-based colloids stabilized by non-drug biocompatible organic molecules, intended for use in nanomedicine

A lab-on-a-disc platform enables serial monitoring of individual CTCs associated with tumor progression during EGFR-targeted therapy for patients with NSCLC

Rationale: Unlike traditional biopsy, liquid biopsy, which is a largely non-invasive diagnostic and monitoring tool, can be performed more frequently to better track tumors and mutations over time and to validate the efficiency of a cancer treatment. Circulating tumor cells (CTCs) are considered promising liquid biopsy biomarkers; however, their use in clinical settings is limited by high costs and a low throughput of standard platforms for CTC enumeration and analysis. In this study, we used a label-free, high-throughput method for CTC isolation directly from whole blood of patients using a standalone, clinical setting-friendly platform. Methods: A CTC-based liquid biopsy approach was used to examine the efficacy of therapy and emergent drug resistance via longitudinal monitoring of CTC counts, DNA mutations, and single-cell-level gene expression in a prospective cohort of 40 patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer. Results: The change ratio of the CTC counts was associated with tumor response, detected by CT scan, while the baseline CTC counts did not show association with progression-free survival or overall survival. We achieved a 100% concordance rate for the detection of EGFR mutation, including emergence of T790M, between tumor tissue and CTCs. More importantly, our data revealed the importance of the analysis of the epithelial/mesenchymal signature of individual pretreatment CTCs to predict drug responsiveness in patients. Conclusion: The fluid-assisted separation technology disc platform enables serial monitoring of CTC counts, DNA mutations, as well as unbiased molecular characterization of individual CTCs associated with tumor progression during targeted therapy

Computational Approach to Identify Enzymes That Are Potential Therapeutic Candidates for Psoriasis

Psoriasis is well known as a chronic inflammatory dermatosis. The disease affects persons of all ages and is a burden worldwide. Psoriasis is associated with various diseases such as arthritis. The disease is characterized by well-demarcated lesions on the skin of the elbows and knees. Various genetic and environmental factors are related to the pathogenesis of psoriasis. In order to identify enzymes that are potential therapeutic targets for psoriasis, we utilized a computational approach, combining microarray analysis and protein interaction prediction. We found 6,437 genes (3,264 upregulated and 3,173 downregulated) that have significant differences in expression between regions with and without lesions in psoriasis patients. We identified potential candidates through protein-protein interaction predictions made using various protein interaction resources. By analyzing the hub protein of the networks with metrics such as degree and centrality, we detected 32 potential therapeutic candidates. After filtering these candidates through the ENZYME nomenclature database, we selected 5 enzymes: DNA helicase (RUVBL2), proteasome endopeptidase complex (PSMA2), nonspecific protein-tyrosine kinase (ZAP70), I-kappa-B kinase (IKBKE), and receptor protein-tyrosine kinase (EGFR). We adopted a computational approach to detect potential therapeutic targets; this approach may become an effective strategy for the discovery of new drug targets for psoriasis

Metabolic engineering of a reduced-genome strain of Escherichia coli for L-threonine production

© 2009 Lee et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens