An automated method to quantify and visualize colocalized fluorescent signals

Background: Recent studies have linked synaptojanin 1 (synj1) with Alzheimer disease (AD). Results: We report that synj1 reduction decreases amyloid plaque burden and attenuates cognitive deterioration in an AD mouse model. These effects are mediated through accelerating endosomal/lysosomal degradation of A␤. Conclusion: Our data suggest a novel mechanism by which synj1 reduction promotes A␤ clearance. Significance: These studies implicate a therapeutic strategy for AD.

Section: Methodsmentioning

confidence: 99%

Reduction of Synaptojanin 1 Accelerates Aβ Clearance and Attenuates Cognitive Deterioration in an Alzheimer Mouse Model

Zhu

Zhong

Zhao

et al. 2013

“…This software is based on a previously published algorithm (12). The correlation of a pair of pixels was calculated by the normalized mean deviation product (nMDP) as follows,…”

Section: Methodsmentioning

confidence: 99%

An Engineered Glutamate-gated Chloride (GluCl) Channel for Sensitive, Consistent Neuronal Silencing by Ivermectin

Frazier

Cohen

Lester

2013

Background: Ivermectin (IVM) silences activity in neurons expressing glutamate-gated chloride channels (GluCl). Results: Rational point mutations in GluCl robustly increase IVM-induced conductance and reduce the variability of spike suppression in cultured neurons. Conclusion:The newly engineered receptor improves heteromeric receptor expression and sensitivity to IVM. Significance: GluClv2.0 is an improved tool for IVM-induced silencing.

“…For co-localization analysis, all image data were preprocessed prior to quantification by means of an iterative constrained Tikhonov-Miller algorithm (DeconvolutionLab ImageJ plugin (24)) to reduce the blurring from nearby bright objects and the out-of-focus noise. Co-localization was evaluated using the Colocalization Colormap script, an ImageJ plugin for automated quantification and visualization of co-localized fluorescent signals (25). The method computes correlation of intensities between pairs of individual pixels in two different channels.…”

Section: Methodsmentioning

confidence: 99%

The CD157-Integrin Partnership Controls Transendothelial Migration and Adhesion of Human Monocytes

Buono¹,

Parrotta²,

Morone³

et al. 2011

CD157, a member of the CD38 gene family, is an NAD-metabolizing ectoenzyme and a signaling molecule whose role in polarization, migration, and diapedesis of human granulocytes has been documented; however, the molecular events underpinning this role remain to be elucidated. This study focused on the role exerted by CD157 in monocyte migration across the endothelial lining and adhesion to extracellular matrix proteins. The results demonstrated that anti-CD157 antibodies block monocyte transmigration and adhesion to fibronectin and fibrinogen but that CD157 cross-linking is sufficient to overcome the block, suggesting an active signaling role for the molecule. Consistent with this is the observation that CD157 is prevalently located within the detergent-resistant membrane microdomains to which, upon clustering, it promotes the recruitment of ␤ 1 and ␤ 2 integrin, which, in turn, leads to the formation of a multimolecular complex favoring signal transduction. This functional cross-talk with integrins allows CD157 to act as a receptor despite its intrinsic structural inability to do so on its own. Intracellular signals mediated by CD157 rely on the integrin/Src/ FAK (focal adhesion kinase) pathway, resulting in increased activity of the MAPK/ERK1/2 and the PI3K/Akt downstream signaling pathways, which are crucial in the control of monocyte transendothelial migration. Collectively, these findings indicate that CD157 acts as a molecular organizer of signaling-competent membrane microdomains and that it forms part of a larger molecular machine ruled by integrins. The CD157-integrin partnership provides optimal adhesion and transmigration of human monocytes.