291 research outputs found
C9ORF72 patient-derived endothelial cells drive blood-brain barrier disruption and contribute to neurotoxicity
The blood-brain barrier (BBB) serves as a highly intricate and dynamic interface connecting the brain and the bloodstream, playing a vital role in maintaining brain homeostasis. BBB dysfunction has been associated with multiple neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS); however, the role of the BBB in neurodegeneration is understudied. We developed an ALS patient-derived model of the BBB by using cells derived from 5 patient donors carrying C9ORF72 mutations. Brain microvascular endothelial-like cells (BMEC-like cells) derived from C9ORF72-ALS patients showed altered gene expression, compromised barrier integrity, and increased P-glycoprotein transporter activity. In addition, mitochondrial metabolic tests demonstrated that C9ORF72-ALS BMECs display a significant decrease in basal glycolysis accompanied by increased basal and ATP-linked respiration. Moreover, our study reveals that C9-ALS derived astrocytes can further affect BMECs function and affect the expression of the glucose transporter Glut-1. Finally, C9ORF72 patient-derived BMECs form leaky barriers through a cell-autonomous mechanism and have neurotoxic properties towards motor neurons
Consistency analysis of a nonbirefringent Lorentz-violating planar model
In this work analyze the physical consistency of a nonbirefringent
Lorentz-violating planar model via the analysis of the pole structure of its
Feynman propagators. The nonbirefringent planar model, obtained from the
dimensional reduction of the CPT-even gauge sector of the standard model
extension, is composed of a gauge and a scalar fields, being affected by
Lorentz-violating (LIV) coefficients encoded in the symmetric tensor
. The propagator of the gauge field is explicitly evaluated
and expressed in terms of linear independent symmetric tensors, presenting only
one physical mode. The same holds for the scalar propagator. A consistency
analysis is performed based on the poles of the propagators. The isotropic
parity-even sector is stable, causal and unitary mode for .
On the other hand, the anisotropic sector is stable and unitary but in general
noncausal. Finally, it is shown that this planar model interacting with a
Higgs field supports compactlike vortex configurations.Comment: 11 pages, revtex style, final revised versio
- …