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A cloaked human stem-cell-derived neural graft capable of functional integration and immune evasion in rodent models

1 month 3 weeks ago
Human pluripotent stem cell (hPSC)-derived therapies are a realistic possibility for numerous disorders, including Parkinson's disease. While generating replacement neurons is achievable, immunosuppressive drug challenges, to prevent rejection, remain. Here we adopted a hPSC line (termed H1-FS-8IM), engineered to overexpress 8 immunomodulatory transgenes, to enable transplant immune evasion. In co-cultures, H1-FS-8IM PSC-derived midbrain neurons evaded rejection by T lymphocytes, natural killer...
Chiara Pavan

Subthalamic nucleus dynamics during executive functioning: Insights from local field potentials in Parkinson's disease

1 month 3 weeks ago
This study explores the involvement of the subthalamic nucleus (STN) in executive functions, particularly cognitive flexibility, in Parkinson's disease (PD) patients. Utilizing a computerized Wisconsin Card Sorting Task (WCST) and local field potential (LFP) recordings from implanted deep brain stimulation (DBS) electrodes, we investigated task-specific neural dynamics. Behavioural results demonstrated increased error rates and prolonged response times in trials requiring set-shifting and rule...
Lejla Paracka

The bridge-like lipid transport protein VPS13C/PARK23 mediates ER-lysosome contacts following lysosome damage

1 month 3 weeks ago
Based on genetic studies, lysosome dysfunction is thought to play a pathogenetic role in Parkinson's disease. Here we show that VPS13C, a bridge-like lipid-transport protein and a Parkinson's disease gene, is a sensor of lysosome stress or damage. Following lysosome membrane perturbation, VPS13C rapidly relocates from the cytosol to the surface of lysosomes where it tethers their membranes to the ER. This recruitment depends on Rab7 and requires a signal at the damaged lysosome surface that...
Xinbo Wang

Expression of anti-amyloid CARs in microglia promotes efficient and selective phagocytosis of Aβ1‒42

1 month 3 weeks ago
Genetic engineering of microglial cells is a promising therapeutic avenue emerging with advancements in gene delivery techniques. Using a recently developed AAV capsid for efficient in vitro transduction we report the engineering of microglia with CARs (CAR-Mic) targeting phagocytosis of amyloid beta 1‒42 (Aβ42). Functional screening of seven CAR constructs in human iPSC-derived microglia revealed up to 6-fold increases in internalized Aβ relative to viral control. CAR-driven phagocytic...
Christina N Heiss

Lower aperiodic EEG activity is associated with reduced verbal fluency performance across adulthood

1 month 3 weeks ago
Age-related cognitive decline associations with human electroencephalography (EEG) have previously focused on periodic activity. However, EEG primarily consists of non-oscillatory aperiodic activity, characterised with an exponent and offset value. In a secondary analysis of a cohort of 111 healthy participants aged 17 - 71 years, we examined the associations of the aperiodic exponent and offset in resting EEG with a battery of cognitive tests consisting of the Colour-Word Interference Test,...
Daniel J McKeown

The role of the three major intestinal barriers in ulcerative colitis in the elderly

1 month 3 weeks ago
With the unprecedented pace of global population aging, there has been a parallel epidemiological shift marked by increasing incidence rates of ulcerative colitis (UC) in geriatric populations, imposing a substantial disease burden on healthcare systems globally. The etiopathogenesis of UC in the elderly remains poorly delineated, while current therapeutic strategies require further optimization to accommodate the unique pathophysiological characteristics of elderly patients. This review...
Min Fu