C5 complement inhibition versus FcRn modulation in generalised myasthenia gravis.

Background: Myasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular junctions, leading to fluctuating muscle weakness. While many patients respond well to standard immunosuppression, a substantial subgroup faces ongoing disease activity. Emerging treatments such as complement factor C5 inhibition (C5IT) and neonatal Fc receptor (FcRn) antagonism hold promise for these patients.

Early-Life Adversity Predicts Markers of Aging-Related Neuroinflammation, Neurodegeneration, and Cognitive Impairment in Women.

Objective: Despite the overwhelming evidence for profound and longstanding effects of early-life stress (ELS) on inflammation, brain structure, and molecular aging, its impact on human brain aging and risk for neurodegenerative disease is poorly understood. We examined the impact of ELS severity in interaction with age on blood-based markers of neuroinflammation and neurodegeneration, brain volumes, and cognitive function in middle-aged women.

Methods: We recruited 179 women (aged 30-60 years) with and without ELS exposure before the onset of puberty.

Activation and Reactivity of the Deubiquitinylase OTU Cezanne-2 from MD Simulations and QM/MM Calculations.

Cezanne-2 (Cez2) is a deubiquitinylating (DUB) enzyme involved in the regulation of ubiquitin-driven cellular signaling and selectively targets Lys11-linked polyubiquitin chains. As a representative member of the ovarian tumor (OTU) subfamily DUBs, it performs cysteine proteolytic isopeptide bond cleavage; however, its exact catalytic mechanism is not yet resolved. In this work, we used different computational approaches to get molecular insights into the Cezanne-2 catalytic mechanism.

Resting State Functional Connectivity of the Default Mode Network During Opioid Use and Cessation in Treatment-Seeking Persons.

Resting-state functional connectivity analyses have been used to examine synchrony in neural networks in substance use disorders (SUDs), with the default mode network (DMN) one of the most studied. Prior research has generally found less DMN synchrony during use and greater synchrony during cessation, although little research has utilized this method with opioid use. This study examined resting brain activity in treatment-seeking persons who use opioids at two points-when using opioids and when opioid-free-to determine whether the DMN exhibits different levels of connectivity during opioid use and cessation and whether differences in connectivity predict subsequent relapse.