Mitochondria and neuroplasticity

The production of neurons from neural progenitor cells, the growth of axons and dendrites and the formation and reorganization of synapses are examples of neuroplasticity. These processes are regulated by cell-autonomous and intercellular (paracrine and endocrine) programs that mediate responses of neural cells to environmental input. Mitochondria are highly mobile and move within and between subcellular compartments involved in neuroplasticity (synaptic terminals, dendrites, cell body and the axon). By generating energy (ATP and NAD+), and regulating subcellular Ca2+ and redox homoeostasis, mitochondria may play important roles in controlling fundamental processes in neuroplasticity, including neural differentiation, neurite outgrowth, neurotransmitter release and dendritic remodelling. Particularly intriguing is emerging data suggesting that mitochondria emit molecular signals (e.g. reactive oxygen species, proteins and lipid mediators) that can act locally or travel to distant targets including the nucleus. Disturbances in mitochondrial functions and signalling may play roles in impaired neuroplasticity and neuronal degeneration in Alzheimer's disease, Parkinson's disease, psychiatric disorders and stroke

The Empirical Research of Factors Influencing Share of Wallet in the B2B Market

Share of wallet is a key factor in Customer relationship management system (CRM) which is an important application of E-business. Research has found that share of wallet is an important indicator to measure customer loyalty and customer potential value. On the basis of the existent marketing literatures, this study analyzes the variables influencing share of wallet according the traits of the B2B market. This paper brings forward interrelated hypotheses and conceptual model, then test the hypotheses with enterprises survey in the B2B market. Finally we use path analysis to find the principal factors influencing share of wallet and the relationships in them. The results of this research provide theoretical foundation to upgrade CRM management level of the B2B enterprises, and there is a certain reference value to predict share of wallet in customer lifetime value’s (CLV) measurement

Roosting habitat selection of Hume's Pheasant (Syrmaticus humiae) in a fragmented forest patch, northwestern Guangxi, southwestern China

Knowledge of roosting site preference has shown a great importance for the conservation of Galliformes. The selection of good roosting habitats may prevent an excessive energy expenditure and reduce the risk of predation. The night roosts selected by two male and two female Hume's Pheasants (Syrmaticus humiae) were studied using radio transmitters in the Jinzhongshan National Nature Reserve, Guangxi, southern China. Thirty-five night roost sites were detected between February and August 2012. Hume's Pheasant roosted in family groups, predominantly in Tung oil tree (Vernicia fordii). The roosting site characteristics of Hume's Pheasant, including the distance to the habitat edge and road, shrub coverage, and height of roost branches between the breeding and non-breeding period showed statistically significant differences (P < 0.05). The factors discriminating roosting habitat selection in the breeding season from that in non-breeding season were: slope position, distance to habitat edge, distance to road, height of roost branch, and height of the lowest branch. Our results suggested that the selection of night roosts is determined by predator avoidance, and energy saving strategies aimed at reducing flight activity and increasing feeding opportunities. Furthermore, roost microclimate seemed to also influence the selection of night roosts. Keywords: Roosting habitat selection, Discriminant analysis, Hume's Pheasan

The N-Terminal 24 Amino Acids of the p55 Gamma Regulatory Subunit of Phosphoinositide 3-Kinase Binds Rb and Induces Cell Cycle Arrest

Although phosphoinositide 3-kinase (PI 3-kinase) is essential for cell cycle progression, the molecular mechanisms that regulate its diverse biological effects are poorly understood. We demonstrate here that Rb, a key regulator of cell cycle progression, associates with p55 kDa (p55α and p55γ) regulatory subunits of PI 3-kinase in vivo and in vitro. Both confocal microscopy and biochemical analysis demonstrated the presence of p55γ in the nucleus. The 24-amino-acid N-terminal end of p55γ, which is unique among PI 3-kinase regulatory subunits, was sufficient to bind Rb. Addition of serum or growth factors to quiescent cells triggered the dissociation of Rb from p55. Ectopic expression of the 24-amino-acid N-terminal end of p55γ inhibited cell cycle progression, as evidenced by induction of cell growth arrest at the G(0)/G(1) phase, inhibition of DNA synthesis, inhibition of cyclin D and cyclin E promoter activity, and changes in the expression of cell cycle-related proteins. The inhibitory effects of the N-terminal end of p55γ on cell cycle progression depended on the presence of functional Rb. These data demonstrate for the first time an association of p55γ with Rb and show that modification of this association can lead to cell cycle arrest

Permeability Transition Pore-Mediated Mitochondrial Superoxide Flashes Regulate Cortical Neural Progenitor Differentiation

<div><p>In the process of neurogenesis, neural progenitor cells (NPCs) cease dividing and differentiate into postmitotic neurons that grow dendrites and an axon, become excitable, and establish synapses with other neurons. Mitochondrial biogenesis and aerobic metabolism provide energy substrates required to support the differentiation, growth and synaptic activity of neurons. Mitochondria may also serve signaling functions and, in this regard, it was recently reported that mitochondria can generate rapid bursts of superoxide (superoxide flashes), the frequency of which changes in response to environmental conditions and signals including oxygen levels and Ca²⁺ fluxes. Here we show that the frequency of mitochondrial superoxide flashes increases as embryonic cerebral cortical neurons differentiate from NPCs, and provide evidence that the superoxide flashes serve a signaling function that is critical for the differentiation process. The superoxide flashes are mediated by mitochondrial permeability transition pore (mPTP) opening, and pharmacological inhibition of the mPTP suppresses neuronal differentiation. Moreover, superoxide flashes and neuronal differentiation are inhibited by scavenging of mitochondrial superoxide. Conversely, manipulations that increase superoxide flash frequency accelerate neuronal differentiation. Our findings reveal a regulatory role for mitochondrial superoxide flashes, mediated by mPTP opening, in neuronal differentiation.</p> </div

Mitochondrial mass and function changes in NPCs during differentiation.

<p>(A, B and C) Mitochondrial mass, measured by Mitotracker green loading (A), mitochondrial ATP content (B) and mitochondrial superoxide production, evaluated by MitoSOXred loading (C) are normalized by protein concentration in differentiated cells. (D) Mitochondrial membrane potential (∆Ψm) was imaged by mitoCMXros loading in NPCs on differentiation days 0, 2 and 4. Bar = 20 µm. (E) Mitochondrial membrane potential (∆Ψm) was determined by the ratio of MitoCMXros to Mitotracker green intensity. Values are expressed as a percentage of the mean of NPCs at day 0 (n = 4 separate experiments performed on NPCs cultured from 4 pregnant mice) *p<0.05, **p<0.001 compared to the values of NPCs at day 0.</p

Expression of mitochondrial proteins in NPCs during differentiation.

<p>(A, B and C) Immunoblot analysis was performed by using antibodies that selectively recognize cytochrome c, MnSOD and cyclophylin D. Blots were reprobed with antibodies against Actin. Panel A shows representative blots; panels B and C show results of densitometric analysis of cyclophylin D and MnSOD, which were normalized to the corresponding mitochondrial cytochrome c level on each differentiation day. Values are expressed as a percentage of the mean of NPCs at day 0 (n = 3-4 separate experiments performed on cells cultured from 3-4 pregnant mice); *p<0.05 compared to the values of NPCs at day 0.</p