Interplay between Cell Migration and Neurite Outgrowth Determines SH2B1β-Enhanced Neurite Regeneration of Differentiated PC12 Cells

The regulation of neurite outgrowth is crucial in developing strategies to promote neurite regeneration after nerve injury and in degenerative diseases. In this study, we demonstrate that overexpression of an adaptor/scaffolding protein SH2B1β promotes neurite re-growth of differentiated PC12 cells, an established neuronal model, using wound healing (scraping) assays. Cell migration and the subsequent remodeling are crucial determinants during neurite regeneration. We provide evidence suggesting that overexpressing SH2B1β enhances protein kinase C (PKC)-dependent cell migration and phosphatidylinositol 3-kinase (PI3K)-AKT-, mitogen activated protein kinase (MAPK)/extracellular signal-regulated protein kinase (ERK) kinase (MEK)-ERK-dependent neurite re-growth. Our results further reveal a cross-talk between pathways involving PKC and ERK1/2 in regulating neurite re-growth and cell migration. We conclude that temporal regulation of cell migration and neurite outgrowth by SH2B1β contributes to the enhanced regeneration of differentiated PC12 cells

Effective gauge group of pure loop quantum gravity is SO(3): New estimate of the Immirzi parameter

We argue that the effective gauge group for {\it pure} four-dimensional loop quantum gravity(LQG) is SO(3) (or $SO(3,C)$) instead of SU(2) (or $SL(2,C)$). As a result, links with half-integer spins in spin network states are not realized for {\it pure} LQG, implying a modification of the spectra of area and volume operators. Our observations imply a new value of $\gamma \approx 0.170$ for the Immirzi parameter which is obtained from matching the Bekenstein-Hawking entropy to the number of states from LQG calculations. Moreover, even if the dominant contribution to the entropy is not assumed to come from configurations with the minimum spins, the results of both pure LQG and the supersymmetric extension of LQG can be made compatible when only integer spins are realized for the former, while the latter also contains half-integer spins, together with an Immirzi parameter for the supersymmetric case which is twice the value of the SO(3) theory. We also verify that the $-{1/2}$ coefficient of logarithmic correction to the Bekenstein-Hawking entropy formula is robust, independent of whether only integer, or also half-integer spins, are realized.Comment: new value of Immirzi parameter is ~0.170; dominance of miminum spin configurations is not assumed in comparing with Bekenstein-Hawking formula; typos corrected. Version pressed in PL

Distribution and associated factors of optic disc diameter and cup-to-disc ratio in an elderly Chinese population

AbstractBackgroundGlaucoma is the second leading cause of blindness worldwide and East Asian people account for almost half of those affected. Vertical elongation of the optic cup is a characteristic feature of glaucoma. However, there is a significant overlap in the vertical cup-to-disc ratio (VCDR) between normal eyes and eyes affected by glaucoma. The purpose of this study was to determine the distribution of VCDR and vertical disc diameter (VDD) and their predictive factors in a population of elderly Chinese residents in Taiwan.MethodsFour hundred and sixty elderly Chinese residents aged 72 years and older in the Shihpai district, Taipei, Taiwan participated in this study. Slit lamp biomicroscopic measurement of the VCDR and VDD after pupil dilation with a 78 diopter lens was performed by one glaucoma specialist. Multiple linear regression analyses were used to fit the best model for independent variables.ResultsThe VCDR was recorded for 438 right eyes and 430 left eyes. After excluding participants with glaucoma, the mean ± SD VCDR was 0.44 ± 0.17 for both eyes, and the 97.5th percentile was 0.8. A greater VCDR was associated with a longer axial length [VCDR = −0.47 + 0.04(axial length)] under multiple regression analysis. The VDD was obtained for 420 right eyes and 406 left eyes. The mean ± SD VDD for all participants was 1.77 ± 0.22 mm for the right eye and 1.79 ± 0.22 mm for the left eye. A higher body mass index (BMI) and a longer axial length were significantly associated with a larger VDD under multiple regression analysis. [VDD = −0.05 + 0.07 (axial length) + 0.06 (obesity); if BMI <24, then obesity = 0; if BMI ≥24, then obesity = 1]. A larger VDD was associated with a larger VCDR (p < 0.001) and the VCDR could be predicted by the equation VCDR = −0.07 + 0.3VDD.ConclusionA greater VCDR was related to a longer axial length. A greater VDD was related to a higher BMI and a longer axial length

Socioeconomic impacts of innovative dairy supply chain practices. The case of the Laiterie du Berger in the Senegalese Sahel

This study analyzes the Laiterie Du Berger (LDB)'s milk supply chain and its contribution to strengthening the food security and socioeconomic resources of Senegalese Sahelian pastoral households. Porter's value chain model is used to characterize the innovations introduced by the LDB dairy in its milk inbound logistics and supplier relationships. A socioeconomic food security index and qualitative data are used to assess the dairy's supply chain's contribution to strengthen smallholder households' livelihoods. Data for this research were obtained through individual surveys, focus groups and in-depth interviews of LDB managers and milk suppliers. Results show that milk income contributes significantly to household food security. Suppliers who stabilize their dairy income between rainy and dry seasons, diversify income sources and have larger herds are more likely to remain food secure. The LDB innovations contribute by helping herders access biophysical and economic resources, leading to better livestock feed and household food security. (Résumé d'auteur

HTLV-1 Tax mutants that do not induce G1 arrest are disabled in activating the anaphase promoting complex

HTLV-1 Tax is a potent activator of viral transcription and NF-κB. Recent data indicate that Tax activates the anaphase promoting complex/cyclosome (APC/C) ahead of schedule, causing premature degradation of cyclin A, cyclin B1, securin, and Skp2. Premature loss of these mitotic regulators is accompanied by mitotic aberrations and leads to rapid senescence and cell cycle arrest in HeLa and S. cerevisiae cells. Tax-induced rapid senescence (tax-IRS) of HeLa cells is mediated primarily by a dramatic stabilization of p27KIP and is also accompanied by a great surge in the level of p21CIP1mRNA and protein. Deficiencies in p27KIP prevent Tax-IRS. A collection of tax point mutants that permit normal growth of S. cerevisiae have been isolated. Like wild-type tax, many of them (C23W, A108T, L159F, and L235F) transactivate both the HTLV-LTR and the NF-κB reporters. One of them, V19M, preferentially activates NF-κB, but is attenuated for LTR activation. None of the mutants significantly elevated the levels of p21CIP1and p27KIP1, indicating that the dramatic surge in p21CIP1/WAF1and p27KIP 1induced by Tax is brought about by a mechanism distinct from NF-κB or LTR activation. Importantly, the ability of these mutants to activate APC/C is attenuated or abrogated. These data indicate that Tax-induced rapid senescence is causally associated with APC/C activation

Light-Independent Inactivation of Dengue-2 Virus by Carboxyfullerene C3 Isomer

AbstractCarboxyfullerene (C60) is known as a photosensitizer for virus inactivation. Its regioisomer with C3 symmetry, named the C3 isomer, could also inactivate the dengue-2 virus without light when the dose of C3 isomer was increased to 40 μM, indicating the possible involvement of a light-independent mechanism. Further analysis showed that the C3 isomer blocked viral replication at the attachment and penetration stages, suggesting that a direct interaction between the C3 isomer and the virion is required for inactivation. The C3 isomer with a bipolar structure showed better lipid interaction and dengue-2 virus suppression than D3, another isomer that contains evenly distributed hydrophilic side chains. Moreover, the C3 isomer selectively inactivated enveloped viruses (viz., dengue-2 virus and Japanese encephalitis virus) instead of nonenveloped viruses (viz., enterovirus 71 and coxsackievirus B3). Collectively, these findings support the hypothesis that C3 isomer suppression of enveloped viruses is effected through its hydrophobic interaction with the viral lipid envelope. Our report, which demonstrates the light-dependent and -independent mechanisms of C60 on viral inactivation, will aid in the development of novel anti-viral agents for use against enveloped viruses