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

Transport properties of Co2CrAl Heusler alloy films

The effect of atomic disorder on the electron transport and the magnetoresistance (MR) of Co2CrAl Heusler alloy (HA) films has been investigated. We show that Co2CrAl films with L21 order exhibit a negative value for the temperature coefficient of resistivity (TCR) in a temperature range of 10 < T <  290 K, and the temperature dependence of electric conductivity varies as T3/2 similarly to that of the zero-gap semiconductors. The atomic or the site disorder on the way of L21 →  B2  →  A2  →  amorphous state in Co2CrAl HA films causes the deviation from this dependence: reduction in the absolute value of TCR as well as decrease in the resistivity down to ϱ(T = 293 K)  ~  200 μΩ cm in comparison to ϱ(T = 293 K)  ~  230 μΩ cm typical for the Co2CrAl films with L21 order. The magnetic-field dependence of MR of the Co2CrAl films with L21 order is determined by two competing contributions: a positive Lorentz scattering and a negative s-d scattering. The atomic disorder in Co2CrAl films drastically changes MR behavior due to its strong influence on the magnetic properties