KATP channels are necessary for glucose-dependent increases in amyloid-β and Alzheimer's disease-related pathology.

Elevated blood glucose levels, or hyperglycemia, can increase brain excitability and amyloid-β (Aβ) release, offering a mechanistic link between type 2 diabetes and Alzheimer's disease (AD). Since the cellular mechanisms governing this relationship are poorly understood, we explored whether ATP-sensitive potassium (KATP) channels, which couple changes in energy availability with cellular excitability, play a role in AD pathogenesis. First, we demonstrate that KATP channel subunits Kir6.

Photoinduced charge transfer in the Zn-methanol cation studied with selected-ion photofragment imaging.

The Zn(methanol) ion molecule complex produced by laser vaporization is studied with photofragment imaging at 280 and 266 nm. Photodissociation produces the methanol cation CHOH via excitation of a charge-transfer excited state. Surprisingly, excitation of bound excited states produces the same fragment via a curve crossing prior to separation of products.

Results of the phase I CCTG IND.231 trial of CX-5461 in patients with advanced solid tumors enriched for DNA-repair deficiencies.

CX-5461 is a G-quadruplex stabilizer that exhibits synthetic lethality in homologous recombination-deficient models. In this multicentre phase I trial in patients with solid tumors, 40 patients are treated across 10 dose levels (50-650 mg/m) to determine the recommended phase II dose (primary outcome), and evaluate safety, tolerability, pharmacokinetics (secondary outcomes). Defective homologous recombination is explored as a predictive biomarker of response.

Photofragment Imaging of Carbon Cluster Cations: Explosive Ring Rupture.

Carbon cluster cations (C) produced by laser vaporization are mass selected and photodissociated at 355 nm. Multiphoton dissociation of smaller ions leads to the elimination of neutral C, as in previous work, whereas larger clusters exhibit more varied fragmentation channels. Photofragment velocity-map imaging detects significant kinetic energy release (KER) in the various - 3 cation fragments.

Intranasal insulin modulates cerebrospinal fluid markers of neuroinflammation in mild cognitive impairment and Alzheimer's disease: a randomized trial.

Intranasal insulin (INI) has shown promise as a treatment for Alzheimer's disease (AD) in pilot clinical trials. In a recent phase 2 trial, participants with mild cognitive impairment (MCI) or AD who were treated with INI with one of two delivery devices showed improved cerebral spinal fluid (CSF) biomarker profiles and slower symptom progression compared with placebo. In the cohort which showed benefit, we measured changes in CSF markers of inflammation, immune function and vascular integrity and assessed their relationship with changes in cognition, brain volume, and CSF amyloid and tau concentrations.