Apolipoprotein E4 impairs the response of neurodegenerative retinal microglia and prevents neuronal loss in glaucoma.

The apolipoprotein E4 (APOE4) allele is associated with an increased risk of Alzheimer disease and a decreased risk of glaucoma, but the underlying mechanisms remain poorly understood. Here, we found that in two mouse glaucoma models, microglia transitioned to a neurodegenerative phenotype characterized by upregulation of Apoe and Lgals3 (Galectin-3), which were also upregulated in human glaucomatous retinas. Mice with targeted deletion of Apoe in microglia or carrying the human APOE4 allele were protected from retinal ganglion cell (RGC) loss, despite elevated intraocular pressure (IOP).

Epitope identification of SARS-CoV-2 structural proteins using in silico approaches to obtain a conserved rational immunogenic peptide.

The short time between the first cases of COVID-19 and the declaration of a pandemic initiated the search for ways to stop the spread of SARS-CoV-2. There are great expectations regarding the development of effective vaccines that protect against all variants, and in the search for it, we hypothesized the obtention of a predicted rational immunogenic peptide from structural components of SARS-CoV-2 might help the vaccine research direction. In the search for a candidate of an immunogenic peptide of the SARS-CoV-2 envelope (E), membrane (M), nucleocapsid (N), or spike (S) proteins, we access the predicted sequences of each protein after the genome sequenced worldwide.

Pharmacological profiling of JME-173, a novel mexiletine derivative combining dual anti-inflammatory/anti-spasmodic functions and limited action in Na channels.

Existing evidence suggests that the local anaesthetic mexiletine can be beneficial for patients with asthma. However, caution is required since anaesthesia of the airways inhibits protective bronchodilator neuronal reflexes, limiting applications in conditions of hyperirritable airways. Here, we describe the synthesis of a new series of mexiletine analogues, which were screened for reduced activity in Na channels and improved smooth muscle relaxant effects, that were evaluated using the patch-clamp technique and an isolated tracheal organ bath, respectively.

Characterization and engineering of a plastic-degrading aromatic polyesterase.

Poly(ethylene terephthalate) (PET) is one of the most abundantly produced synthetic polymers and is accumulating in the environment at a staggering rate as discarded packaging and textiles. The properties that make PET so useful also endow it with an alarming resistance to biodegradation, likely lasting centuries in the environment. Our collective reliance on PET and other plastics means that this buildup will continue unless solutions are found.

Sex-Specific Effects of Adiponectin on Carotid Intima-Media Thickness and Incident Cardiovascular Disease.

Background: Plasma adiponectin levels have previously been inversely associated with carotid intima-media thickness (IMT), a marker of subclinical atherosclerosis. In this study, we used a sex-stratified Mendelian randomization approach to investigate whether adiponectin has a causal protective influence on IMT.

Methods And Results: Baseline plasma adiponectin concentration was tested for association with baseline IMT, IMT progression over 30 months, and occurrence of cardiovascular events within 3 years in 3430 participants (women, n=1777; men, n=1653) with high cardiovascular risk but no prevalent disease.

Central precocious puberty that appears to be sporadic caused by paternally inherited mutations in the imprinted gene makorin ring finger 3.

Context: Loss-of-function mutations in makorin ring finger 3 (MKRN3), an imprinted gene located on the long arm of chromosome 15, have been recognized recently as a cause of familial central precocious puberty (CPP) in humans. MKRN3 has a potential inhibitory effect on GnRH secretion.

Objectives: The objective of the study was to investigate potential MKRN3 sequence variations as well as copy number and methylation abnormalities of the 15q11 locus in patients with apparently sporadic CPP.

Serum 25-hydroxyvitamin D concentration in subclinical carotid atherosclerosis.

Objective: Vitamin D deficiency has been implicated in cardiovascular disease and is associated with multiple cardiovascular risk factors. We investigated the serum 25-hydroxyvitamin D (25(OH)D) concentration in relation to latitude, baseline carotid intima-media thickness (IMT), and IMT progression, the carotid IMT measures being surrogate markers of subclinical atherosclerosis and cardiovascular disease risk.

Approach And Results: Serum 25(OH)D concentration was related to high-resolution carotid IMT measures in 3430 middle-aged and elderly subjects with high cardiovascular risk but no prevalent disease, who were recruited at 7 centers in Finland, Sweden, The Netherlands, France, and Italy.

Molecular and ultrastructural profiles of the symbionts in Cephalotes ants.

The molecular and ultrastructural profiles of the symbionts found in the midgut and ileum of Cephalotes atratus, Cephalotes clypeatus, and Cephalotes pusillus were determined using the V3 region of the bacterial 16S rDNA gene and transmission electron microscopy (T.E.M.