Aligned electrospun fibers for neural patterning

OBJECTIVES: To test a 3D approach for neural network formation, alignment, and patterning that is reproducible and sufficiently stable to allow for easy manipulation. RESULTS: A novel cell culture system was designed by engineering a method for the directional growth of neurons. This uses NG108-15 neuroblastoma x glioma hybrid cells cultured on suspended and aligned electrospun fibers. These fiber networks improved cellular directionality, with alignment angle standard deviations significantly lower on fibers than on regular culture surfaces. Morphological studies found nuclear aspect ratios and cell projection lengths to be unchanged, indicating that cells maintained neural morphology while growing on fibers and forming a 3D network. Furthermore, fibronectin-coated fibers enhanced neurite extensions for all investigated time points. Differentiated neurons exhibited significant increases in average neurite lengths 96 h post plating, and formed neurite extensions parallel to suspended fibers, as visualized through scanning electron microscopy. CONCLUSIONS: The developed model has the potential to serve as the basis for advanced 3D studies, providing an original approach to neural network patterning and setting the groundwork for further investigations into functionality

Ambipolar Field Effect in Topological Insulator Nanoplates of (BixSb1-x)2Te3

Topological insulators represent a new state of quantum matter attractive to both fundamental physics and technological applications such as spintronics and quantum information processing. In a topological insulator, the bulk energy gap is traversed by spin-momentum locked surface states forming an odd number of surface bands that possesses unique electronic properties. However, transport measurements have often been dominated by residual bulk carriers from crystal defects or environmental doping which mask the topological surface contribution. Here we demonstrate (BixSb1-x)2Te3 as a tunable topological insulator system to manipulate bulk conductivity by varying the Bi/Sb composition ratio. (BixSb1-x)2Te3 ternary compounds are confirmed as topological insulators for the entire composition range by angle resolved photoemission spectroscopy (ARPES) measurements and ab initio calculations. Additionally, we observe a clear ambipolar gating effect similar to that observed in graphene using nanoplates of (BixSb1-x)2Te3 in field-effect-transistor (FET) devices. The manipulation of carrier type and concentration in topological insulator nanostructures demonstrated in this study paves the way for implementation of topological insulators in nanoelectronics and spintronics.Comment: 7 pages, 4 figure

The Merging of Two Dynasties—Identification of an African Cotton Leaf Curl Disease-Associated Begomovirus with Cotton in Pakistan

Cotton leaf curl disease (CLCuD) is a severe disease of cotton that occurs in Africa and Pakistan/northwestern India. The disease is caused by begomoviruses in association with specific betasatellites that differ between Africa and Asia. During survey of symptomatic cotton in Sindh (southern Pakistan) Cotton leaf curl Gezira virus (CLCuGV), the begomovirus associated with CLCuD in Africa, was identified. However, the cognate African betasatellite (Cotton leaf curl Gezira betasatellite) was not found. Instead, two Asian betasatellites, the CLCuD-associated Cotton leaf curl Multan betasatellite (CLCuMB) and Chilli leaf curl betasatellite (ChLCB) were identified. Inoculation of the experimental plant species Nicotiana benthamiana showed that CLCuGV was competent to maintain both CLCuMB and ChLCB. Interestingly, the enations typical of CLCuD were only induced by CLCuGV in the presence of CLCuMB. Also in infections involving both CLCuMB and ChLCB the enations typical of CLCuMB were less evident. This is the first time an African begomovirus has been identified on the Indian sub-continent, highlight the growing threat of begomoviruses and particularly the threat of CLCuD causing viruses to cotton cultivation in the rest of the world

Regeneration of Pancreatic Non-β Endocrine Cells in Adult Mice following a Single Diabetes-Inducing Dose of Streptozotocin

The non-β endocrine cells in pancreatic islets play an essential counterpart and regulatory role to the insulin-producing β-cells in the regulation of blood-glucose homeostasis. While significant progress has been made towards the understanding of β-cell regeneration in adults, very little is known about the regeneration of the non-β endocrine cells such as glucagon-producing α-cells and somatostatin producing δ-cells. Previous studies have noted the increase of α-cell composition in diabetes patients and in animal models. It is thus our hypothesis that non-β-cells such as α-cells and δ-cells in adults can regenerate, and that the regeneration accelerates in diabetic conditions. To test this hypothesis, we examined islet cell composition in a streptozotocin (STZ)-induced diabetes mouse model in detail. Our data showed the number of α-cells in each islet increased following STZ-mediated β-cell destruction, peaked at Day 6, which was about 3 times that of normal islets. In addition, we found δ-cell numbers doubled by Day 6 following STZ treatment. These data suggest α- and δ-cell regeneration occurred rapidly following a single diabetes-inducing dose of STZ in mice. Using in vivo BrdU labeling techniques, we demonstrated α- and δ-cell regeneration involved cell proliferation. Co-staining of the islets with the proliferating cell marker Ki67 showed α- and δ-cells could replicate, suggesting self-duplication played a role in their regeneration. Furthermore, Pdx1+/Insulin− cells were detected following STZ treatment, indicating the involvement of endocrine progenitor cells in the regeneration of these non-β cells. This is further confirmed by the detection of Pdx1+/glucagon+ cells and Pdx1+/somatostatin+ cells following STZ treatment. Taken together, our study demonstrated adult α- and δ-cells could regenerate, and both self-duplication and regeneration from endocrine precursor cells were involved in their regeneration

hEGR1 is induced by EGF, inhibited by gefitinib in bladder cell lines and related to EGF receptor levels in bladder tumours

The effect of EGF and gefitinib on two EGFR-positive human bladder cancer cell lines has been investigated using array-based gene expression profiling. The most prominent transcript, increased up to 6.7-fold by EGF compared with controls in RT112 cells, was human early growth response protein 1 (hEGR1). This induction was prevented by gefitinib. The hEGR1 mRNA in EGF-treated samples was reduced in the presence of gefitinib, as was hEGR1 protein in cell lysates. In the RT4 cells, hEGR1 expression was halved in the presence of EGF and gefitinib in combination. In bladder tumour samples, there was a significant correlation between hEGR1 mRNA detected by RT-PCR and EGFR detected by ligand binding, (P=0.042). The induction by EGF of the hEGR1 gene, mRNA and protein in RT112 cells, and its inhibition by gefitinib, together with the detection of hEGR1 mRNA in bladder tumours, suggests that hEGR1 may be important in the EGFR growth-signalling pathway in bladder cancer and should be further investigated for its prognostic significance and as a potential therapeutic target

Extracting expression modules from perturbational gene expression compendia

<p>Abstract</p> <p>Background</p> <p>Compendia of gene expression profiles under chemical and genetic perturbations constitute an invaluable resource from a systems biology perspective. However, the perturbational nature of such data imposes specific challenges on the computational methods used to analyze them. In particular, traditional clustering algorithms have difficulties in handling one of the prominent features of perturbational compendia, namely partial coexpression relationships between genes. Biclustering methods on the other hand are specifically designed to capture such partial coexpression patterns, but they show a variety of other drawbacks. For instance, some biclustering methods are less suited to identify overlapping biclusters, while others generate highly redundant biclusters. Also, none of the existing biclustering tools takes advantage of the staple of perturbational expression data analysis: the identification of differentially expressed genes.</p> <p>Results</p> <p>We introduce a novel method, called ENIGMA, that addresses some of these issues. ENIGMA leverages differential expression analysis results to extract expression modules from perturbational gene expression data. The core parameters of the ENIGMA clustering procedure are automatically optimized to reduce the redundancy between modules. In contrast to the biclusters produced by most other methods, ENIGMA modules may show internal substructure, i.e. subsets of genes with distinct but significantly related expression patterns. The grouping of these (often functionally) related patterns in one module greatly aids in the biological interpretation of the data. We show that ENIGMA outperforms other methods on artificial datasets, using a quality criterion that, unlike other criteria, can be used for algorithms that generate overlapping clusters and that can be modified to take redundancy between clusters into account. Finally, we apply ENIGMA to the Rosetta compendium of expression profiles for <it>Saccharomyces cerevisiae </it>and we analyze one pheromone response-related module in more detail, demonstrating the potential of ENIGMA to generate detailed predictions.</p> <p>Conclusion</p> <p>It is increasingly recognized that perturbational expression compendia are essential to identify the gene networks underlying cellular function, and efforts to build these for different organisms are currently underway. We show that ENIGMA constitutes a valuable addition to the repertoire of methods to analyze such data.</p

Receptor-Mediated Endocytosis of α-Galactosidase A in Human Podocytes in Fabry Disease

Injury to the glomerular podocyte is a key mechanism in human glomerular disease and podocyte repair is an important therapeutic target. In Fabry disease, podocyte injury is caused by the intracellular accumulation of globotriaosylceramide. This study identifies in the human podocyte three endocytic receptors, mannose 6-phosphate/insulin-like growth II receptor, megalin, and sortilin and demonstrates their drug delivery capabilities for enzyme replacement therapy. Sortilin, a novel α-galactosidase A binding protein, reveals a predominant intracellular expression but also surface expression in the podocyte. The present study provides the rationale for the renal effect of treatment with α-galactosidase A and identifies potential pathways for future non-carbohydrate based drug delivery to the kidney podocyte and other potential affected organs