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1.
IEEE Trans Vis Comput Graph ; 18(2): 214-27, 2012 Feb.
Article in English | MEDLINE | ID: mdl-21383404

ABSTRACT

We present a process to automatically generate three-dimensional mesh representations of the complex, arborized cell membrane surface of cortical neurons (the principal information processing cells of the brain) from nonuniform morphological measurements. Starting from manually sampled morphological points (3D points and diameters) from neurons in a brain slice preparation, we construct a polygonal mesh representation that realistically represents the continuous membrane surface, closely matching the original experimental data. A mapping between the original morphological points and the newly generated mesh enables simulations of electrophysiolgical activity to be visualized on this new membrane representation. We compare the new mesh representation with the state of the art and present a series of use cases and applications of this technique to visualize simulations of single neurons and networks of multiple neurons.


Subject(s)
Image Processing, Computer-Assisted/methods , Models, Neurological , Neuroimaging/methods , Neurons/cytology , Neurons/physiology , Algorithms , Animals , Brain/cytology , Computer Simulation , Electrophysiological Phenomena , Humans , Nerve Net/cytology , Nerve Net/physiology , Reproducibility of Results
2.
Nature ; 456(7219): 250-4, 2008 Nov 13.
Article in English | MEDLINE | ID: mdl-18830243

ABSTRACT

The integrity of the cornea, the most anterior part of the eye, is indispensable for vision. Forty-five million individuals worldwide are bilaterally blind and another 135 million have severely impaired vision in both eyes because of loss of corneal transparency; treatments range from local medications to corneal transplants, and more recently to stem cell therapy. The corneal epithelium is a squamous epithelium that is constantly renewing, with a vertical turnover of 7 to 14 days in many mammals. Identification of slow cycling cells (label-retaining cells) in the limbus of the mouse has led to the notion that the limbus is the niche for the stem cells responsible for the long-term renewal of the cornea; hence, the corneal epithelium is supposedly renewed by cells generated at and migrating from the limbus, in marked opposition to other squamous epithelia in which each resident stem cell has in charge a limited area of epithelium. Here we show that the corneal epithelium of the mouse can be serially transplanted, is self-maintained and contains oligopotent stem cells with the capacity to generate goblet cells if provided with a conjunctival environment. Furthermore, the entire ocular surface of the pig, including the cornea, contains oligopotent stem cells (holoclones) with the capacity to generate individual colonies of corneal and conjunctival cells. Therefore, the limbus is not the only niche for corneal stem cells and corneal renewal is not different from other squamous epithelia. We propose a model that unifies our observations with the literature and explains why the limbal region is enriched in stem cells.


Subject(s)
Adult Stem Cells/cytology , Epithelium, Corneal/cytology , Multipotent Stem Cells/cytology , Animals , Cattle , Cells, Cultured , Child, Preschool , Clone Cells , Corneal Transplantation , Epithelium, Corneal/metabolism , Female , Gene Expression Regulation , Humans , Infant , Keratinocytes/cytology , Keratinocytes/metabolism , Male , Mice , Mice, SCID , Models, Biological , Proteins/metabolism , Rats , Swine
3.
J Virol ; 79(16): 10460-6, 2005 Aug.
Article in English | MEDLINE | ID: mdl-16051838

ABSTRACT

The infectious particles of hepatitis B virus (HBV) and hepatitis delta virus (HDV) are coated with the large, middle, and small envelope proteins encoded by HBV. While it is clear that the N-terminal pre-S1 domain of the large protein, which is exposed at the virion surface, is implicated in binding to a cellular receptor at viral entry, the role in infectivity of the envelope protein antigenic loop, also exposed to the virion surface and accessible to neutralizing antibodies, remains to be established. In the present study, mutations were created in the antigenic loop of the three envelope proteins, and the resulting mutants were evaluated for their capacity to assist in the maturation and infectivity of HDV. We observed that short internal combined deletions and insertions, affecting residues 109 to 133 in the antigenic loop, were tolerated for secretion of both subviral HBV particles and HDV virions. However, when assayed for infectivity on primary cultures of human hepatocytes or on the recently described HepaRG cell line, virions carrying deletions between residues 118 and 129 were defective. Single amino acid substitutions in this region revealed that Gly-119, Pro-120, Cys-121, Arg-122, and Cys-124 were instrumental in viral entry. These results demonstrate that in addition to a receptor-binding site previously identified in the pre-S1 domain of the L protein, a determinant of infectivity resides in the antigenic loop of HBV envelope proteins.


Subject(s)
Hepatitis B virus/chemistry , Hepatitis Delta Virus/pathogenicity , Viral Envelope Proteins/chemistry , Amino Acid Motifs , Amino Acid Sequence , Amino Acid Substitution , Cell Line , Humans , Molecular Sequence Data , Structure-Activity Relationship , Viral Envelope Proteins/immunology , Viral Envelope Proteins/physiology
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