Small Molecule Drug C381 Attenuates Brain Vascular Damage Following Repetitive Mild Traumatic Injury.

Traumatic brain injury (TBI) remains a significant public health concern, with no effective therapeutic interventions to ameliorate the enduring consequences. The prevailing understanding of TBI pathophysiology indicates a central role for vascular dysfunction. Transforming growth factor-β (TGF-β) is a multifunctional cytokine crucial for vascular development.

Human tNeurons reveal aging-linked proteostasis deficits driving Alzheimer's phenotypes.

Aging is a prominent risk factor for Alzheimer's disease (AD), but the cellular mechanisms underlying neuronal phenotypes remain elusive. Both accumulation of amyloid plaques and neurofibrillary tangles in the brain and age-linked organelle deficits are proposed as causes of AD phenotypes but the relationship between these events is unclear. Here, we address this question using a transdifferentiated neuron (tNeuron) model directly from human dermal fibroblasts.

Proteostasis and lysosomal repair deficits in transdifferentiated neurons of Alzheimer's disease.

Aging is the most prominent risk factor for Alzheimer's disease (AD). However, the cellular mechanisms linking neuronal proteostasis decline to the characteristic aberrant protein deposits in AD brains remain elusive. Here, we develop transdifferentiated neurons (tNeurons) from human dermal fibroblasts as a neuronal model that retains aging hallmarks and exhibits AD-linked vulnerabilities.

A constant pressure flowmeter for extreme-high vacuum.

We demonstrate operation of a constant-pressure flowmeter capable of generating and accurately measuring flows as low as 2 × 10 mol/s. Generation of such small flows is accomplished by using a small conductance element with ≈ 50 nL/s. Accurate measurement then requires both low outgassing materials (< 1 × 10 mol/s) and small volume changes (≈ 70 L).

Small molecule C381 targets the lysosome to reduce inflammation and ameliorate disease in models of neurodegeneration.

SignificanceNeurodegenerative diseases are poorly understood and difficult to treat. One common hallmark is lysosomal dysfunction leading to the accumulation of aggregates and other undegradable materials, which cause damage to brain resident cells. Lysosomes are acidic organelles responsible for breaking down biomolecules and recycling their constitutive parts.