Impairment of lipid homeostasis causes lysosomal accumulation of endogenous protein aggregates through ESCRT disruption.

Protein aggregation increases during aging and is a pathological hallmark of many age-related diseases. Protein homeostasis (proteostasis) depends on a core network of factors directly influencing protein production, folding, trafficking, and degradation. Cellular proteostasis also depends on the overall composition of the proteome and numerous environmental variables.

Targeting the aminopeptidase ERAP enhances antitumor immunity by disrupting the NKG2A-HLA-E inhibitory checkpoint.

The aminopeptidase, endoplasmic reticulum aminopeptidase 1 (ERAP1), trims peptides for loading into major histocompatibility complex class I (MHC class I), and loss of this activity has broad effects on the MHC class I peptidome. Here, we investigated the impact of targeting ERAP1 in immune checkpoint blockade (ICB), as MHC class I interactions mediate both activating and inhibitory functions in antitumor immunity. Loss of ERAP sensitized mouse tumor models to ICB, and this sensitivity depended on CD8 T cells and natural killer (NK) cells.

Plasma and Kidney Proteome Profiling Combined with Laser Capture Microdissection Reveal Large Increases in Immunoglobulins with Age.

One of the main hallmarks of aging is aging-associated inflammation, also known as inflammaging. In this study, by comparing plasma and kidney proteome profiling of young and old mice using LC-MS profiling, we discovered that immunoglobulins are the proteins that exhibit the highest increase with age. This observation seems to have been disregarded because conventional proteome profiling experiments typically overlook the expression of high-abundance proteins or employ depletion methods to remove them before LC-MS analysis.

A data analysis framework for combining multiple batches increases the power of isobaric proteomics experiments.

We present a framework for the analysis of multiplexed mass spectrometry proteomics data that reduces estimation error when combining multiple isobaric batches. Variations in the number and quality of observations have long complicated the analysis of isobaric proteomics data. Here we show that the power to detect statistical associations is substantially improved by utilizing models that directly account for known sources of variation in the number and quality of observations that occur across batches.

Incidence of bony Bankart lesions in Sweden: a study of 790 cases from the Swedish fracture register.

Background: A bony Bankart lesion directly affects the stability of the shoulder by reducing the glenoid joint-contact area. The aim of this study was to report on the epidemiological data relating to bony Bankart lesions in Sweden using the Swedish fracture register. The purpose is to evaluate age and sex distribution in the population with bony Bankart lesions, its impact on treatment strategy and further to analyse patient-reported outcomes.