Altered Cellular Metabolism Is a Consequence of Loss of the Ataxia-Linked Protein Sacsin.

Mitochondrial dysfunction is implicated in the pathogenesis of the neurological condition autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), yet precisely how the mitochondrial metabolism is affected is unknown. Thus, to better understand changes in the mitochondrial metabolism caused by loss of the sacsin protein (encoded by the SACS gene, which is mutated in ARSACS), we performed mass spectrometry-based tracer analysis, with both glucose- and glutamine-traced carbon. Comparing the metabolite profiles between wild-type and sacsin-knockout cell lines revealed increased reliance on aerobic glycolysis in sacsin-deficient cells, as evidenced by the increase in lactate and reduction of glucose.

alters the lipid droplet proteome and modulates droplet dynamics.

Excess lipid droplet (LD) accumulation is associated with several pathological states, including Alzheimer's disease (AD). However, the mechanism(s) by which changes in LD composition and dynamics contribute to pathophysiology of these disorders remains unclear. Apolipoprotein E (ApoE) is a droplet associated protein with a common risk variant (E4) that confers the largest increase in genetic risk for late-onset AD.

Anti-gene oligonucleotide clamps invade dsDNA and downregulate expression.

Anti-gene oligonucleotides belong to a group of therapeutic compounds, which, in contrast to antisense oligonucleotides, bind to DNA. Clamp anti-gene oligonucleotides bind through a double-stranded invasion mechanism. With two arms connected by a linker, they hybridize to one of the DNA strands forming Watson-Crick and Hoogsteen hydrogen bonds.

Core Outcome Set development for LEPtospirosis trials (COS-LEP): a study protocol to develop a core outcome set for the evaluation of clinical therapeutic interventions for human leptospirosis.

Background: Leptospirosis is a zoonotic bacterial infection occurring worldwide. It is of particular public health concern due to its global distribution, epidemic potential and high mortality without appropriate treatment. The method for the management of leptospirosis, particularly in severe disease, is clouded by methodological inconsistency and a lack of standardized outcome measures.

Reconstruction Kernel Optimization for Ultra-High-Resolution Photon-Counting Detector Computed Tomography of the Lung.

Background: The latest generation of computed tomography (CT) systems based on photon-counting detector promises significant improvements in several clinical applications, including chest imaging.

Purpose: The aim of the study is to evaluate the image quality of ultra-high-resolution (UHR) photon-counting detector CT (PCD-CT) of the lung using four sharp reconstruction kernels.

Material And Methods: This retrospective study included 25 patients (11 women and 14 men; median age, 71 years) who underwent unenhanced chest CT from April to May 2023.