Recurrent mutation in confirms dysregulated sphingolipid production to cause juvenile amyotrophic lateral sclerosis.

Background: Amyotrophic lateral sclerosis (ALS) leads to paralysis and death by progressive degeneration of motor neurons. Recently, specific mutations in were identified in patients with juvenile form of ALS encodes the second catalytic subunit of the serine-palmitoyltransferase (SPT) complex.

Methods: We used the GENESIS platform to screen 700 ALS whole-genome and whole-exome data sets for variants in .

Genetic Causes of Vascular Malformations and Common Signaling Pathways Involved in Their Formation.

The identification of the genetic cause of vascular malformations is improving understanding of pathogenesis of these lesions and also informing potential opportunities for treatment. Somatic activating mutations affecting RAS/MAPK and PIK3/AKT/mTor pathways are implicated in all types of vascular malformations. Pathogenic variants associated with vascular lesions may be germline or somatic.

Genetic Risk Factors for Alzheimer's Disease in Racial/Ethnic Minority Populations in the U.S.: A Scoping Review.

As the United States (U.S.) population rapidly ages, the incidence of Alzheimer's Disease and Related Dementias (ADRDs) is rising, with racial/ethnic minorities affected at disproportionate rates.

Enhancing membrane repair increases regeneration in a sciatic injury model.

Various injuries to the neural tissues can cause irreversible damage to multiple functions of the nervous system ranging from motor control to cognitive function. The limited treatment options available for patients have led to extensive interest in studying the mechanisms of neuronal regeneration and recovery from injury. Since many neurons are terminally differentiated, by increasing cell survival following injury it may be possible to minimize the impact of these injuries and provide translational potential for treatment of neuronal diseases.

Multiple poloxamers increase plasma membrane repair capacity in muscle and nonmuscle cells.

Various previous studies established that the amphiphilic tri-block copolymer known as poloxamer 188 (P188) or Pluronic-F68 can stabilize the plasma membrane following a variety of injuries to multiple mammalian cell types. This characteristic led to proposals for the use of P188 as a therapeutic treatment for various disease states, including muscular dystrophy. Previous studies suggest that P188 increases plasma membrane integrity by resealing plasma membrane disruptions through its affinity for the hydrophobic lipid chains on the lipid bilayer.

Lipidomic Adaptations in White and Brown Adipose Tissue in Response to Exercise Demonstrate Molecular Species-Specific Remodeling.

Exercise improves whole-body metabolic health through adaptations to various tissues, including adipose tissue, but the effects of exercise training on the lipidome of white adipose tissue (WAT) and brown adipose tissue (BAT) are unknown. Here, we utilize MS/MS shotgun lipidomics to determine the molecular signatures of exercise-induced adaptations to subcutaneous WAT (scWAT) and BAT. Three weeks of exercise training decrease specific molecular species of phosphatidic acid (PA), phosphatidylcholines (PC), phosphatidylethanolamines (PE), and phosphatidylserines (PS) in scWAT and increase specific molecular species of PC and PE in BAT.