Understanding Glucagon Aggregation: In Silico Insights and Experimental Validation.

Peptide aggregation poses a significant challenge in biopharmaceutical development and neurodegenerative diseases. This study combines computational simulations and experimental validation to uncover the underlying mechanisms and countermeasures for the aggregation of glucagon, a peptide with a high tendency to aggregate. In silico simulations demonstrate that lactose and 2-hydroxypropyl-β-cyclodextrin (2-HPβCD) influence glucagon aggregation differently: lactose stabilizes glucagon by increasing the α-helical content, while 2-HPβCD disrupts protein-protein interactions.

Advancement of microfluidic modulation spectroscopy as a highly sensitive protein characterization technique for the detection of small structural changes.

The higher order structure (HOS) of a protein is vital to its function and activity, making it a critical component in the development of protein-based therapeutics. Characterization of HOS can be performed using various biophysical techniques, but many of these methods have limitations such as low throughput, complicated workflow, narrow concentration range, and low sensitivity. Microfluidic Modulation Spectroscopy (MMS) is an emerging technology that addresses these limitations, offering high sensitivity and automated analysis for protein secondary structure.

OnabotulinumtoxinA significantly attenuates bladder afferent nerve firing and inhibits ATP release from the urothelium.

Objective: To investigate the direct effect of onabotulinumtoxinA (OnaBotA) on bladder afferent nerve activity and release of ATP and acetylcholine (ACh) from the urothelium.

Materials And Methods: Bladder afferent nerve activity was recorded using an in vitro mouse preparation enabling simultaneous recordings of afferent nerve firing and intravesical pressure during bladder distension. Intraluminal and extraluminal ATP, ACh, and nitric oxide (NO) release were measured using the luciferin-luciferase and Amplex(®) Red assays (Molecular Probes, Carlsbad, CA, USA), and fluorometric assay kit, respectively.

The afferent system and its role in lower urinary tract dysfunction.

Purpose Of Review: Lower urinary tract disorders such as overactive bladder syndrome (OABS) and interstitial cystitis/painful bladder syndrome (IC/PBS) are debilitating conditions with serious adverse effects on quality of life. Common to both OABS and IC/PBS are the sensory symptoms of urgency and frequency, implicating the afferent system in the aetiology of these disorders. Thus, understanding the role that afferent pathways play in the function of the lower urinary tract is the focus of much current research.

The basolateral expression of mUT-A3 in the mouse kidney.

Facilitative UT-A urea transporters play a central role in the urinary concentrating mechanism. There are three major UT-A isoforms found in the mouse kidney: mUT-A1, mUT-A2, and mUT-A3. The major aim of this study was to identify the location and function of mUT-A3.