Fastrac Engine: Understanding Technical Implications of Programmatic Decisions

No abstract availabl

Molecular compartmentalization of lateral geniculate nucleus in the gray squirrel (Sciurus carolinensis)

Previous research has suggested that the three physiologically defined relay cell-types in mammalian lateral geniculate nucleus (LGN)—called parvocellular (P), magnocellular (M), and koniocellular (K) cells in primates and X, Y, and W cells in other mammals—each express a unique combination of cell-type marker proteins. However, some of the relationships among physiological classification and protein expression found in primates, prosimians, and tree shrews do not apply to carnivores and murid rodents. It remains unknown whether these are exceptions to a common rule for all mammals, or whether these relationships vary over a wide range of species. To address this question, we examined protein expression in the gray squirrel (Sciurus carolinensis), a highly visual rodent. Unlike many rodents, squirrel LGN is well laminated, and the organization of X-like, Y-like, and W-like cells relative to the LGN layers has been characterized physiologically. We labeled tissue sections through visual thalamus with antibodies to calbindin and parvalbumin, the antibody Cat-301, and the lectin WFA. Calbindin expression was found in W-like cells in LGN layer 3, just adjacent to the optic tract. These results suggest that calbindin is a common marker for the konicellular pathway in mammals. However, while parvalbumin expression characterizes P and M cells in primates and X and Y cells in tree shrews, here it identifies only about half of the X-like cells in LGN layers 1 and 2. Putative Y/M cell markers did not differentiate relay cells in this animal. Together, these results suggest that protein expression patterns among LGN relay cell classes are variable across mammals

Opening Day

Although I've read and written poetry for my own pleasure for about twenty years now, I've only seriously studied and written poetry on a consistent basis for the past two years. In this sense, I still consider myself a beginning poet. When attempting to pursue an art form as refined and historically informed as poetry, only after spending a number of years reading and writing intensively would I no longer consider myself a beginner, but a practitioner of the art. I've grounded my early development as a poet in concision, voice, and imagination, and hope to build upon these ideas with other poetic techniques, theories, and forms as I go forward. I am particularly interested in mastering the sonnet form, a concise and imaginative form that will allow me to further develop my skills. Hopefully, the works in this thesis reflect that effort

Past NASA Program Experiences Enable Future Government and Industry Successes

No abstract availabl

Limits and dynamics of stochastic neuronal networks with random heterogeneous delays

Realistic networks display heterogeneous transmission delays. We analyze here the limits of large stochastic multi-populations networks with stochastic coupling and random interconnection delays. We show that depending on the nature of the delays distributions, a quenched or averaged propagation of chaos takes place in these networks, and that the network equations converge towards a delayed McKean-Vlasov equation with distributed delays. Our approach is mostly fitted to neuroscience applications. We instantiate in particular a classical neuronal model, the Wilson and Cowan system, and show that the obtained limit equations have Gaussian solutions whose mean and standard deviation satisfy a closed set of coupled delay differential equations in which the distribution of delays and the noise levels appear as parameters. This allows to uncover precisely the effects of noise, delays and coupling on the dynamics of such heterogeneous networks, in particular their role in the emergence of synchronized oscillations. We show in several examples that not only the averaged delay, but also the dispersion, govern the dynamics of such networks.Comment: Corrected misprint (useless stopping time) in proof of Lemma 1 and clarified a regularity hypothesis (remark 1

Ki-67 is a PP1-interacting protein that organises the mitotic chromosome periphery

Copyright @ 2014 Booth et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.When the nucleolus disassembles during open mitosis, many nucleolar proteins and RNAs associate with chromosomes, establishing a perichromosomal compartment coating the chromosome periphery. At present nothing is known about the function of this poorly characterised compartment. In this study, we report that the nucleolar protein Ki-67 is required for the assembly of the perichromosomal compartment in human cells. Ki-67 is a cell-cycle regulated protein phosphatase 1-binding protein that is involved in phospho-regulation of the nucleolar protein B23/nucleophosmin. Following siRNA depletion of Ki-67, NIFK, B23, nucleolin, and four novel chromosome periphery proteins all fail to associate with the periphery of human chromosomes. Correlative light and electron microscopy (CLEM) images suggest a near-complete loss of the entire perichromosomal compartment. Mitotic chromosome condensation and intrinsic structure appear normal in the absence of the perichromosomal compartment but significant differences in nucleolar reassembly and nuclear organisation are observed in post-mitotic cells

Expression and Functional Studies on the Noncoding RNA, PRINS.

PRINS, a noncoding RNA identified earlier by our research group, contributes to psoriasis susceptibility and cellular stress response. We have now studied the cellular and histological distribution of PRINS by using in situ hybridization and demonstrated variable expressions in different human tissues and a consistent staining pattern in epidermal keratinocytes and in vitro cultured keratinocytes. To identify the cellular function(s) of PRINS, we searched for a direct interacting partner(s) of this stress-induced molecule. In HaCaT and NHEK cell lysates, the protein proved to be nucleophosmin (NPM) protein as a potential physical interactor with PRINS. Immunohistochemical experiments revealed an elevated expression of NPM in the dividing cells of the basal layers of psoriatic involved skin samples as compared with healthy and psoriatic uninvolved samples. Others have previously shown that NPM is a ubiquitously expressed nucleolar phosphoprotein which shuttles to the nucleoplasm after UV-B irradiation in fibroblasts and cancer cells. We detected a similar translocation of NPM in UV-B-irradiated cultured keratinocytes. The gene-specific silencing of PRINS resulted in the retention of NPM in the nucleolus of UV-B-irradiated keratinocytes; suggesting that PRINS may play a role in the NPM-mediated cellular stress response in the skin

Pharmacological and rAAV Gene Therapy Rescue of Visual Functions in a Blind Mouse Model of Leber Congenital Amaurosis

BACKGROUND: Leber congenital amaurosis (LCA), a heterogeneous early-onset retinal dystrophy, accounts for ~15% of inherited congenital blindness. One cause of LCA is loss of the enzyme lecithin:retinol acyl transferase (LRAT), which is required for regeneration of the visual photopigment in the retina. METHODS AND FINDINGS: An animal model of LCA, the Lrat (−/−) mouse, recapitulates clinical features of the human disease. Here, we report that two interventions—intraocular gene therapy and oral pharmacologic treatment with novel retinoid compounds—each restore retinal function to Lrat (−/−) mice. Gene therapy using intraocular injection of recombinant adeno-associated virus carrying the Lrat gene successfully restored electroretinographic responses to ~50% of wild-type levels (p < 0.05 versus wild-type and knockout controls), and pupillary light responses (PLRs) of Lrat (−/−) mice increased ~2.5 log units (p < 0.05). Pharmacological intervention with orally administered pro-drugs 9-cis-retinyl acetate and 9-cis-retinyl succinate (which chemically bypass the LRAT-catalyzed step in chromophore regeneration) also caused long-lasting restoration of retinal function in LRAT-deficient mice and increased ERG response from ~5% of wild-type levels in Lrat (−/−) mice to ~50% of wild-type levels in treated Lrat (−/−) mice (p < 0.05 versus wild-type and knockout controls). The interventions produced markedly increased levels of visual pigment from undetectable levels to 600 pmoles per eye in retinoid treated mice, and ~1,000-fold improvements in PLR and electroretinogram sensitivity. The techniques were complementary when combined. CONCLUSION: Intraocular gene therapy and pharmacologic bypass provide highly effective and complementary means for restoring retinal function in this animal model of human hereditary blindness. These complementary methods offer hope of developing treatment to restore vision in humans with certain forms of hereditary congenital blindness

Phosphorylation-induced Rearrangement of the Histone H3 NH2-terminal Domain during Mitotic Chromosome Condensation

The NH2-terminal domain (N-tail) of histone H3 has been implicated in chromatin compaction and its phosphorylation at Ser10 is tightly correlated with mitotic chromosome condensation. We have developed one mAb that specifically recognizes histone H3 N-tails phosphorylated at Ser10 (H3P Ab) and another that recognizes phosphorylated and unphosphorylated H3 N-tails equally well (H3 Ab). Immunocytochemistry with the H3P Ab shows that Ser10 phosphorylation begins in early prophase, peaks before metaphase, and decreases during anaphase and telophase. Unexpectedly, the H3 Ab shows stronger immunofluorescence in mitosis than interphase, indicating that the H3 N-tail is more accessible in condensed mitotic chromatin than in decondensed interphase chromatin. In vivo ultraviolet laser cross-linking indicates that the H3 N-tail is bound to DNA in interphase cells and that binding is reduced in mitotic cells. Treatment of mitotic cells with the protein kinase inhibitor staurosporine causes histone H3 dephosphorylation and chromosome decondensation. It also decreases the accessibility of the H3 N-tail to H3 Ab and increases the binding of the N-tail to DNA. These results indicate that a phosphorylation-dependent weakening of the association between the H3 N-tail and DNA plays a role in mitotic chromosome condensation