Search

Midbrain dopaminergic (DA) neurons are the key to finely tune the voluntary movement, habit and motivation. The progressive and selective degeneration of these neurons is a pathological hallmark of Parkinson’s disease (PD). The susceptibility of DA neurons in the SNpc may result from differences in how Ca 2+ is handled. However, very little information is available about the mechanisms involved in the regulation of intracellular Ca 2+ concentration ([Ca 2+ ] i ) in DA neurons. In this study, the relative contributions of various Na + /Ca 2+ exchangers and their interplay with internal Ca 2+ stores, endoplasmic reticulum (ER) and the mitochondria, in the regulation of the [Ca 2+ ] i of mouse mesencephalic neurons were characterized. Both the K + -dependent Na + /Ca 2+ exchanger (NCKX) and the K + -independent Na + /Ca 2+ exchanger (NCX) can be detected and are functional in DA and non-DA neurons. NCX accounts for the larger component of Na + /Ca 2+ exchange activity. Single-cell RT-PCR analysis showed each individual neuron expressed a distinct set of the Na + /Ca 2+ exchangers. Furthermore, the Na + /Ca 2+ exchangers play prominent roles in removing [Ca 2+ ] i induced by glutamate but not [Ca 2+ ] i induced by depolarization. The mitochondria serve as a major Ca 2+ sink and are functionally located close to NCX. In contrast, the ER is functionally located close to NCKX and acts primarily as a Ca 2+ source with marginal effects. This study reveals that the Na + /Ca 2+ exchangers, the ER and the mitochondria, which cooperate interactively, act similarly when regulating [Ca 2+ ] i in mesencephalic DA and non-DA neurons. The heterogeneous expression of multiple types of Na + /Ca 2+ exchangers and the quantitative differences found in [Ca 2+ ] i regulation, together with other risk factors specific to DA neurons such as dopamine oxidation resulting in oxidative stress, may drive these cells to undergo selective degeneration. [ABSTRACT FROM AUTHOR]

The bioactivity screening of fractions from two inter-tidal sponges collected from the north of China Yellow Sea and one sponge collected from the South Chinese Sea was reported in this study. In sponge Hymeniacidon perleve there were 9 fractions out of 15 from CHCl3 extract with anti Staphylococcus aureus activity, 9 fractions out of 19 from BuOH extract with anti Escherichia coli activity, and three fractions from CHCl3 extract which had moderate to strong activity in inhibiting Bacillus subtilis, Candida albicans, and Aspergilus niger. The fractions of Reniochalina sp. showed bioactivity against bacteria and fungi. The fractions of Acanthella acuta Schmidt showed bioactivity against S. aureus and fungi. One compound from H. perleve obtained by the bioactively directing isolation was tested for bioactivity against the human hepatoma cell line Qgy7701 (IC50 10.1 μg/ml), Burkitt''s lymphoma cell line Raji (IC50 9.76 μg/ml) and chronic myelogenous leukemia K562 (IC50 1.90 μg/ml). [Copyright &y& Elsevier]

A single nanomaterial with multiple imaging contrasts and functions is highly desired for multiscale theragnosis. Herein, we demonstrate single 1–1.9 μm infrared-active FePt alloy nanoparticles (FePt NPs) offering unprecedented four-contrast-in-one molecular imaging – computed tomography (CT), magnetic resonance imaging (MRI), photoacoustic (PA) imaging, and high-order multiphoton luminescence (HOMPL) microscopy. The PA response of FePt NPs outperforms that of infrared-active gold nanorods by 3- to 5.6-fold under identical excitation fluence and particle concentrations. HOMPL (680 nm) of an isolated FePt NP renders spatial full-width-at-half-maximum values of 432 nm and 300 nm beyond the optical diffraction limit for 1230-nm and 920-nm excitation, respectively. The in vivo targeting function was successfully visualized using HOMPL, PA imaging, CT, and MRI, thereby validating FePt as a single nanomaterial system covering up to four types (Optical/PA/CT/MRI) of molecular imaging contrast, ranging from the microscopic level to whole-body scale investigation. [ABSTRACT FROM AUTHOR]