Daniel D Lee | PubMed Health

PubMed2026

Brain perivascular macrophages regulate endothelial cell function via a cMAF-dependent transcriptional program in mouse and human.

Brain perivascular macrophages maintain brain physiology, yet their transcriptional regulators and functions in health and disease remain unclear. Using single-cell multi-omics and functional experiments, we identify cellular musculoaponeurotic fibrosarcoma oncogene (cMAF) as a key transcription factor for brain perivascular macrophages, and conditional deletion of cMAF disrupts their phenotype in vivo. Functionally, cMAF drives insulin-like growth factor-1 (IGF1) expression in perivascular macrophages, enabling communication with endothelial cells. Consistently, cMAF deletion in perivascular macrophages causes transcriptional alterations in cerebral arteries, affecting vascular functions. Notably, cMAF emerges as the main transcription factor for human perivascular macrophages, suggesting conservation of this transcriptional module. During Alzheimer's disease (AD), human perivascular macrophages upregulate cMAF and IGF1 to enhance communication with vascular cells, and this response is abrogated in APOE4 carriers. Lastly, we explore an uncharacterized polymorphism in cMAF, providing evidence that the cMAF program is protective against AD. Targeting cMAF in perivascular macrophages may offer new therapeutic strategies for neurodegenerative and cerebrovascular diseases.

APOE4↗

PubMed2004

Short-term memory in orthogonal neural networks.

We study the ability of linear recurrent networks obeying discrete time dynamics to store long temporal sequences that are retrievable from the instantaneous state of the network. We calculate this temporal memory capacity for both distributed shift register and random orthogonal connectivity matrices. We show that the memory capacity of these networks scales with system size.

Memory, Short-Term↗

PubMedDate not supplied

A biomechanical assessment of disc pressures in the lumbosacral spine in response to external unloading forces.

BACKGROUND CONTEXT: Axial back pain affects a large percentage of the population. Often aggravated by weight-bearing activity, these patients frequently have associated degenerative or post-traumatic lumbar disc disease. Aquatherapy is frequently used to transition patients from less activity limited by pain to greater activity by reducing weight-bearing load of the lumbar spine. Development of a means to permit patients similar spinal unloading while active during normal daily living would have the potential to promote similar effects. PURPOSE: The purpose of this study is to measure internal disc pressure at L4/L5 in response to forces exerted by an external vest. The study hypothesis anticipated an unloading of the lumbar spine during upright posture, as measured by intradicsal pressure at the L4/5 disc, correlating with external forces provided to the trunk by the device. STUDY DESIGN: A controlled experimental study of spine biomechanical loading was undertaken using isolated cadaver torsos obtained from an approved tissue source. Ages ranged at death with a mean of 65+/-6 years. METHODS: The distractive force created by inflating a set of pneumatic lifters within vests for treatment of low back pain were calibrated in a materials testing machine. Effects of inflation on the disc pressures within the lumbar spine then were tested. A microscopic pressure sensor (Samba, Gothenburg, Sweden) was placed into the nucleus of the L4/L5 disc of six isolated cadaver torsos (1 female, 5 male) using a 15-gauge spinal needle under direct fluoroscopic visualization. The pressure sensor was 0.42 mm in diameter, and had a calibrated response range of 0-7500 mm Hg. A pneumatically actuated lumbar vest was fit snugly to the torso. Each torso was supported in an upright, weight-bearing position for testing. The vest was inflated while the internal disc pressure was monitored and recorded. The data were analyzed to test for correlation between the amount of external unloading force provided by the vest and the intradiscal pressure measured in vitro. RESULTS: Application of external loads between the pelvis and ribcage by the vest demonstrated a maximum mean reduction of internal disc pressure at L4/L5 of 25% when the vest was inflated to a level producing approximately 400 N of effective load. The reduction in disc pressure was significantly different compared with baseline (upright, weight-bearing disc pressure without the vest) for all distraction settings (p<.01) except for the very lowest setting which was significant only at p=.025. CONCLUSIONS: Spinal unloading with an externally applied vest with adequate surface interface is effective in reducing intradiscal pressures. Ambulatory reduction of pressure would permit beneficial reduction of loads and permit patients with weight-bearing intolerance a better quality of life.

Aged↗