Bioluminescence imaging reveals inhibition of tumor cell proliferation by Alzheimer's amyloid β protein

Background: Cancer and Alzheimer's disease (AD) are two seemingly distinct diseases and rarely occur simultaneously in patients. To explore molecular determinants differentiating pathogenic routes towards AD or cancer, we investigate the role of amyloid β protein (Aβ) on multiple tumor cell lines that are stably expressing luciferase (human glioblastoma U87; human breast adenocarcinoma MDA-MB231; and mouse melanoma B16F). Results: Quantification of the photons emitted from the MDA-MB231 or B16F cells revealed a significant inhibition of cell proliferation by the conditioning media (CM) derived from amyloid precursor protein (APP) over-expressing cells. The inhibition of U87 cells was observed only after the media was conditioned for longer than 2 days with APP over-expressing cells. Conclusion: Our results suggest that Aβ plays an inhibitory role in tumor cell proliferation; this effect could depend on the type of tumor cells and amount of Aβ

Dyadic plasticity in cardiomyocytes

Contraction of cardiomyocytes is dependent on sub-cellular structures called dyads, where invaginations of the surface membrane (t-tubules) form functional junctions with the sarcoplasmic reticulum (SR). Within each dyad, Ca2+ entry through t-tubular L-type Ca2+ channels (LTCCs) elicits Ca2+ release from closely apposed Ryanodine Receptors (RyRs) in the SR membrane. The efficiency of this process is dependent on the density and macroscale arrangement of dyads, but also on the nanoscale organization of LTCCs and RyRs within them. We presently review accumulating data demonstrating the remarkable plasticity of these structures. Dyads are known to form gradually during development, with progressive assembly of both t-tubules and junctional SR terminals, and precise trafficking of LTCCs and RyRs. While dyads can exhibit compensatory remodeling when required, dyadic degradation is believed to promote impaired contractility and arrythmogenesis in cardiac disease. Recent data indicate that this plasticity of dyadic structure/function is dependent on the regulatory proteins junctophilin-2, amphiphysin-2 (BIN1), and caveolin-3, which critically arrange dyadic membranes while stabilizing the position and activity of LTCCs and RyRs. Indeed, emerging evidence indicates that clustering of both channels enables “coupled gating”, implying that nanoscale localization and function are intimately linked, and may allow fine-tuning of LTCC-RyR crosstalk. We anticipate that improved understanding of dyadic plasticity will provide greater insight into the processes of cardiac compensation and decompensation, and new opportunities to target the basic mechanisms underlying heart disease

Femtosecond Laser-Induced Phase Transformation on Single-Crystal 6H-SiC

Silicon carbide (SiC) is widely used in many research fields because of its excellent properties. The femtosecond laser has been proven to be an effective method for achieving high-quality and high-efficiency SiC micromachining. In this article, the ablation mechanism irradiated on different surfaces of 6H-SiC by a single pulse under different energies was investigated. The changes in material elements and the geometric spatial distribution of the ablation pit were analyzed using micro-Raman spectroscopy, Energy Dispersive Spectrum (EDS), and an optical microscope, respectively. Moreover, the thresholds for structural transformation and modification zones of 6H-SiC on different surfaces were calculated based on the diameter of the ablation pits created by a femtosecond laser at different single-pulse energies. Experimental results show that the transformation thresholds of the Si surface and the C surface are 5.60 J/cm2 and 6.40 J/cm2, corresponding to the modification thresholds of 2.26 J/cm2 and 2.42 J/cm2, respectively. The Raman and EDS results reveal that there are no phase transformations or material changes on different surfaces of 6H-SiC at low energy, however, decomposition and oxidation occur and then accumulate into dense new phase material under high-energy laser irradiation. We found that the distribution of structural phase transformation is uneven from the center of the spot to the edge. The content of this research reveals the internal evolution mechanism of high-quality laser processing of hard material 6H-SiC. We expect that this research will contribute to the further development of SiC-based MEMS devices

Bioluminescence imaging reveals inhibition of tumor cell proliferation by Alzheimer's amyloid β protein

Abstract Background Cancer and Alzheimer's disease (AD) are two seemingly distinct diseases and rarely occur simultaneously in patients. To explore molecular determinants differentiating pathogenic routes towards AD or cancer, we investigate the role of amyloid β protein (Aβ) on multiple tumor cell lines that are stably expressing luciferase (human glioblastoma U87; human breast adenocarcinoma MDA-MB231; and mouse melanoma B16F). Results Quantification of the photons emitted from the MDA-MB231 or B16F cells revealed a significant inhibition of cell proliferation by the conditioning media (CM) derived from amyloid precursor protein (APP) over-expressing cells. The inhibition of U87 cells was observed only after the media was conditioned for longer than 2 days with APP over-expressing cells. Conclusion Our results suggest that Aβ plays an inhibitory role in tumor cell proliferation; this effect could depend on the type of tumor cells and amount of Aβ.</p

Intramuscular AAV delivery of NT-3 alters synaptic transmission to motoneurons in adult rats

We examined whether elevating levels of neurotrophin-3 (NT-3) in the spinal cord and dorsal root ganglion (DRG) would alter connections made by muscle spindle afferent fibers on motoneurons. Adeno-associated virus (AAV) serotypes AAV1, AAV2 and AAV5, selected for their tropism profile, were engineered with the NT-3 gene and administered to the medial gastrocnemius muscle in adult rats. ELISA studies in muscle, DRG and spinal cord revealed that NT-3 concentration in all tissues peaked about 3 months after a single viral injection; after 6 months NT-3 concentration returned to normal values. Intracellular recording in triceps surae motoneurons revealed complex electrophysiological changes. Moderate elevation in cord NT-3 resulted in diminished segmental excitatory postsynaptic potential (EPSP) amplitude, perhaps as a result of the observed decrease in motoneuron input resistance. With further elevation in NT-3 expression, the decline in EPSP amplitude was reversed indicating that NT-3 at higher concentration could increase EPSP amplitude. No correlation was observed between EPSP amplitude and NT-3 concentration in the DRG. Treatment with control viruses could elevate NT-3 levels minimally resulting in measurable electrophysiological effects, perhaps as a result of inflammation associated with injection. EPSPs elicited by stimulation of the ventrolateral funiculus underwent a consistent decline in amplitude independent of NT-3 level. These novel correlations between modified NT-3 expression and single-cell electrophysiological parameters indicate that intramuscular administration of AAV(NT-3) can exert long lasting effects on synaptic transmission to motoneurons. This approach to neurotrophin delivery could be useful in modifying spinal function after injury