eyeless/Pax6 controls the production of glial cells in the visual center of Drosophila melanogaster

AbstractPax6 is known as a neurogenic factor in the development of the central nervous system and regulates proliferation of neuronal progenitor cells and promotes neuronal differentiation. In addition to neurogenesis, Pax6 is also involved in the specification and maturation of glial cells. Here, we show that Eyeless (Ey), Drosophila homolog of Pax6, regulates the production of glial cells in the brain. In the developing fly visual center, the production of neurons and glial cells are controlled by the temporal transcription factors that are sequentially expressed in neuroblasts (NBs). Among them, NBs of the last temporal window produce astrocyte-like glial cells. Ey is strongly expressed in the middle aged NBs, whose temporal window is earlier compared with glia producing older NBs. Weak Ey expression is also detected in the glia producing NBs. Our results suggest that Ey expression in the middle aged NBs indirectly control gliogenesis from the oldest NBs by regulating other temporal transcription factors. Additionally, weak Ey expression in the NBs of last temporal window may directly control gliogenesis. Ey is also expressed in neurons produced from the NBs of Ey-positive temporal window. Interestingly, neuron-specific overexpression of Ey causes significant increase in glial cells suggesting that neuronal expression of Ey may also contribute to gliogenesis. Thus, Pax6-dependent regulation of astrocyte-like glial development is conserved throughout the animal kingdom

The dihydropyridine calcium channel blocker benidipine prevents lysophosphatidylcholine-induced endothelial dysfunction in rat aorta

<p>Abstract</p> <p>Background</p> <p>Lysophosphatidylcholine (LPC), an atherogenic component of oxidized low-density lipoprotein, has been shown to induce the attenuation of endothelium-dependent vascular relaxation. Although benidipine, a dihydropyridine-calcium channel blocker, is known to have endothelial protective effects, the effects of benidipine on LPC-induced endothelial dysfunction remain unknown. We examined the effects of benidipine on the impairment of endothelium-dependent relaxation induced by LPC.</p> <p>Methods</p> <p>Benidipine was administered orally to rats and aortas were then isolated. Aortic rings were treated with LPC and endothelial functions were then evaluated. Additionally, the effects of benidipine on intracellular calcium concentration ([Ca²⁺]_i) and membrane fluidity altered by LPC in primary cultured rat aortic endothelial cells were examined. [Ca²⁺]_iwas measured using the fluorescent calcium indicator fura-2. Membrane fluidity was monitored by measuring fluorescence recovery after photobleaching.</p> <p>Results</p> <p>Treatment with LPC impaired endothelial function. Benidipine prevents the impairment of relaxation induced by LPC. Acetylcholine elicited an increase in [Ca²⁺]_iin fura-2 loaded endothelial cells. The increase in [Ca²⁺]_iwas suppressed after exposure to LPC. Plasma membrane fluidity increased following incubation with LPC. Benidipine inhibited the LPC-induced increase in membrane fluidity and impairment of increase in [Ca²⁺]_i.</p> <p>Conclusion</p> <p>These results suggest that benidipine inhibited LPC-induced endothelial dysfunction by maintaining increase in [Ca²⁺]_i. Benidipine possesses membrane stabilization properties in LPC-treated endothelial cells. It is speculated that the preservation of membrane fluidity by benidipine may play a role in the retainment of calcium mobilization. The present findings may provide new insights into the endothelial protective effects of benidipine.</p

Medical Hegemony and Healthcare: Centrality in Healthcare

Better human healthcare is achieved by increasing the fair use and accessibility of medical information. While this optimism is believed, real-world healthcare can be severely affected by the knowledge and context shared in the healthcare industry and academia. Through the sharing process, the central perception gains consensus in the industry and academic societies and standardized therapies are unified and spread quickly. In this way, mainstreamers’ contexts quickly become standardized. Consequently, the mainstream has hegemony and can be strengthened. Mainstreamers neglect any information different from standardized knowledge and therapy. It is universally known that hegemony stabilize its position by undermining the fair use and accessibility of information. The use of patterned knowledge facilitates the utility of medical information. Smart ICT seems to realize the smart use of medical information in our daily lives as well as professional exercises. The method to eliminate such evils and realize true healthcare is required. The fair use and accessibility contribute to the utility of medical knowledge to end-users. The effect and influence of the commons of information are shown as a solution to eliminating adverse events caused by the hegemonic mainstream. As the most effective means in the coming digital healthcare era, this paper shows the following three points. (1) Allow commons of information to enable fair use and search of information. (2) The commons of information release the cognitive bias set by the measure. (3) By creating such a new theory, we will develop a new field called healthcare digital management and/or healthcare digital economics

A temporal mechanism that produces neuronal diversity in the Drosophila visual center

AbstractThe brain consists of various types of neurons that are generated from neural stem cells; however, the mechanisms underlying neuronal diversity remain uncertain. A recent study demonstrated that the medulla, the largest component of the Drosophila optic lobe, is a suitable model system for brain development because it shares structural features with the mammalian brain and consists of a moderate number and various types of neurons. The concentric zones in the medulla primordium that are characterized by the expression of four transcription factors, including Homothorax (Hth), Brain-specific homeobox (Bsh), Runt (Run) and Drifter (Drf), correspond to types of medulla neurons. Here, we examine the mechanisms that temporally determine the neuronal types in the medulla primordium. For this purpose, we searched for transcription factors that are transiently expressed in a subset of medulla neuroblasts (NBs, neuronal stem cell-like neural precursor cells) and identified five candidates (Hth, Klumpfuss (Klu), Eyeless (Ey), Sloppy paired (Slp) and Dichaete (D)). The results of genetic experiments at least explain the temporal transition of the transcription factor expression in NBs in the order of Ey, Slp and D. Our results also suggest that expression of Hth, Klu and Ey in NBs trigger the production of Hth/Bsh-, Run- and Drf-positive neurons, respectively. These results suggest that medulla neuron types are specified in a birth order-dependent manner by the action of temporal transcription factors that are sequentially expressed in NBs

Roles of outer capsid proteins as determinants of pathogenicity and host range restriction of avian rotaviruses in a suckling mouse model

AbstractWe previously demonstrated that a pigeon rotavirus, PO-13, but not turkey strains Ty-3 and Ty-1 and a chicken strain, Ch-1, induced diarrhea in heterologous suckling mice. In this study, it was suggested that these avirulent strains, but not PO-13, were inactivated immediately in gastrointestinal tracts of suckling mice when they were orally inoculated. To determine which viral proteins contribute to the differences between the pathogenicitiy and the inactivation of PO-13 and Ty-3 in suckling mice, six PO-13 × Ty-3 reassortant strains that had the genes of the outer capsid proteins, VP4 and VP7, derived from the opposite strain were prepared and were orally inoculated to suckling mice. A single strain that had both PO-13 VP4 and VP7 with the genetic background of Ty-3 had an intermediate virulence for suckling mice. Three strains with Ty-3 VP7, regardless of the origin of VP4, rapidly disappeared from gastrointestinal tracts of suckling mice. These results indicated that the difference between the pathogenicity of PO-13 and that of Ty-3 was mainly dependent on both their VP4 and VP7. In particular, VP7 was found to be related to the inactivation of Ty-3 in gastrointestinal tracts of suckling mice