USP8 inhibition regulates autophagy flux and controls infection.

Introduction: Ubiquitination is an important protein modification that regulates various essential cellular processes, including the functions of innate immune cells. Deubiquitinases are enzymes responsible for removing ubiquitin modification from substrates, and the regulation of deubiquitinases in macrophages during infection with Typhimurium and remains unknown.

Methods: To identify deubiquitinases regulated in human macrophages during bacterial infection, an activity-based proteomics screen was conducted.

Murine Norovirus Interaction with Enterobacter cloacae Leads to Changes in Membrane Stability and Packaging of Lipid and Metabolite Vesicle Content.

Outer membrane vesicles (OMVs) are a primary means of communication for Gram-negative bacteria. The specific role of vesicle components in cellular communication and how components are packaged are still under investigation, but a correlation exists between OMV biogenesis and content. The two primary mechanisms of OMV biogenesis are membrane blebbing and explosive cell lysis, and vesicle content is based on the biogenesis mechanism.

Using Activity-Based Proteomics for the Quantification of Deubiquitinases in Animal Tissue.

Ubiquitination is a post-translational modification, that regulates essential cellular functions, and the enzymes that control the removal of this modification, deubiquitinases (DUBs), have been well described for the model organisms. However, the information about DUBs is still largely lacking for the non-model organisms, such as agriculturally relevant animals. To understand the expression of these enzymes in animal tissues, we have used chemical proteomics which can be used to identify biologically active DUBs present in tissues based on their reactivity with the activity-based probes (ABPs).

Extracellular vesicles elicit protective immune responses against Salmonella infection.

Small extracellular vesicles (sEVs) produced by antigen-presenting cells represent a novel mechanism of cell-to-cell communication. The sEVs have been shown to drive Th1-type adaptive immune responses against intracellular infections such as Salmonella. In this study, we have demonstrated that an administration of sEVs produced by Salmonella-infected macrophages to BALB/c mice that were then challenged with Salmonella infection decreased bacterial load in infected animals and led to protection against a lethal dose of Salmonella.

Erratum: A CTS Team Approach to Wastewater-Based Epidemiology of Non-Typhoidal Salmonella in Gainesville, FL - ERRATUM.

[This corrects the article DOI: 10.1017/cts.2022.

infection-derived extracellular vesicles drive transcription of genes involved in M2 polarization.

Although it is known that the composition of extracellular vesicles (EVs) is determined by the characteristics of the cell and its environment, the effects of intracellular infection on EV composition and functions are not well understood. We had previously shown that cultured macrophages infected with parasites release EVs (LiEVs) containing parasite-derived molecules. In this study we show that LdVash, a molecule previously identified in LiEVs from infected RAW264.

Bacterial extracellular vesicles control murine norovirus infection through modulation of antiviral immune responses.

Human norovirus is the primary cause of non-bacterial gastroenteritis globally and is the second leading cause of diarrheal deaths in children in developing countries. However, effective therapeutics which prevent or clear norovirus infection are not yet available due to a lack of understanding regarding norovirus pathogenesis. Evidence shows that noroviruses can bind to the surface of commensal bacteria, and the presence of these bacteria alters both acute and persistent murine norovirus infection through the modulation of host immune responses.

Fluorescent Labeling of Small Extracellular Vesicles (EVs) Isolated from Conditioned Media.

Extracellular vesicles (EVs), such as exosomes, are produced by all known eukaryotic cells, and constitute essential means of intercellular communication. Recent studies have unraveled the important roles of EVs in migrating to specific sites and cells. Functional studies of EVs using and systems require tracking these organelles using fluorescent dyes or, alternatively, transfected and fluorescent-tagged proteins, located either intravesicularly or anchored to the EV bilayer membrane.

Current understanding of extracellular vesicle homing/tropism.

Extracellular vesicles (EVs) are membrane-enclosed packets released from cells that can transfer bioactive molecules from cell to cell without direct contact with the target cells. This transfer of molecules can activate consequential processes in the recipient cells, including cell differentiation and migration that maintain tissue homeostasis or promote tissue pathology. One controversial aspect of the EV's biology that holds therapeutic promise is their capacity to engage defined cells at specific sites.

Interaction with mammalian enteric viruses alters outer membrane vesicle production and content by commensal bacteria.

Intestinal commensal bacteria contribute to maintaining gut homeostasis. Disruptions to the commensal flora are linked to the development and persistence of disease. The importance of these organisms is further demonstrated by the widespread ability of enteric viruses to exploit commensal bacteria to enhance viral infection.

Identification of active deubiquitinases in the chicken tissues.

The existing protein annotation in chicken is mostly limited to computational predictions based on orthology to other proteins, which often leads to a significant underestimation of the function of these proteins. Genome-scale experimental annotation can provide insight into the actual enzymatic activities of chicken proteins. Amongst post-translational modifications, ubiquitination is of interest as anomalies in ubiquitination are implicated in such diseases as inflammatory disorders, infectious diseases, or malignancies.

YopJ Limits Macrophage Response by Downregulating COX-2-Mediated Biosynthesis of PGE2 in a MAPK/ERK-Dependent Manner.

Prostaglandin E2 (PGE2) is an essential immunomodulatory lipid released by cells in response to infection with many bacteria, yet its function in macrophage-mediated bacterial clearance is poorly understood. overall inhibits the inflammatory circuit, but its effect on PGE2 production is unknown. We hypothesized that one of the effector proteins is responsible for the inhibition of PGE2 biosynthesis.

Roles of Eicosanoids in Regulating Inflammation and Neutrophil Migration as an Innate Host Response to Bacterial Infections.

Eicosanoids are lipid-based signaling molecules that play a unique role in innate immune responses. The multiple types of eicosanoids, such as prostaglandins (PGs) and leukotrienes (LTs), allow the innate immune cells to respond rapidly to bacterial invaders. Bacterial pathogens alter cyclooxygenase (COX)-derived prostaglandins (PGs) in macrophages, such as PGE2 15d-PGJ, and lipoxygenase (LOX)-derived leukotriene LTB which has chemotactic functions.

Intravacuolar Pathogens Hijack Host Extracellular Vesicle Biogenesis to Secrete Virulence Factors.

Extracellular vesicles (EVs) have garnered significant interest in recent years due to their contributions to cell-to-cell communication and disease processes. EVs are composed of a complex profile of bioactive molecules, which include lipids, nucleic acids, metabolites, and proteins. Although the biogenesis of EVs released by cells under various normal and abnormal conditions has been well-studied, there is incomplete knowledge about how infection influences EV biogenesis.

CNS-Targeting Therapies for Lysosomal Storage Diseases: Current Advances and Challenges.

During the past decades, several therapeutic approaches have been developed and made rapidly available for many patients afflicted with lysosomal storage disorders (LSDs), inborn organelle disorders with broad clinical manifestations secondary to the progressive accumulation of undegraded macromolecules within lysosomes. These conditions are individually rare, but, collectively, their incidence ranges from 1 in 2,315 to 7,700 live-births. Most LSDs are manifested by neurological symptoms or signs, including developmental delay, seizures, acroparesthesia, motor weakness, and extrapyramidal signs.

Characterization and proteomic analysis of outer membrane vesicles from a commensal microbe, Enterobacter cloacae.

Outer membrane vesicles (OMVs) are membrane-enclosed spherical entities released by gram-negative bacteria and are important for bacterial survival under stress conditions. There have been numerous studies on OMVs released by gram-negative pathogenic bacteria, but an understanding of the functions and characteristics of the OMVs produced by commensal microbes is still lacking. Enterobacter cloacae is a gram-negative commensal bacterium present in the human gut microbiome, but this organism can also function as an opportunistic pathogen.

Exosomes released by breast cancer cells under mild hyperthermic stress possess immunogenic potential and modulate polarization in macrophages.

Macrophages play a dual role in tumor initiation and progression, with both tumor-promoting and tumor-suppressive effects; hence, it is essential to understand the distinct responses of macrophages to tumor progression and therapy. Mild hyperthermia has gained importance as a therapeutic regimen against cancer due to its immunogenic nature, efficacy, and potential synergy with other therapies, yet the response of macrophages to molecular signals from hyperthermic cancer cells has not yet been clearly defined. Due to limited response rate of breast cancer to conventional therapeutics the development, and understanding of alternative therapies like hyperthermia is pertinent.

Long-term Changes in the Central Amygdala Proteome in Rats with a History of Chronic Cocaine Self-administration.

The central nucleus of the amygdala (CeA) is a striatum-like structure that contains mainly inhibitory circuits controlling a repertoire of (mal)adaptive behaviors related to pain, anxiety, motivation, and addiction. Neural activity in the CeA is also necessary for the expression of persistent and robust drug seeking, also termed 'incubation of drug craving.' However, neuroadaptations within this brain region supporting incubated drug craving have not been characterized.

An atlas of the catalytically active liver and spleen kinases in chicken identified by chemoproteomics.

Phosphorylation is a post-translational protein modification regulating most known cellular processes. While protein kinases constitute a large family of highly conserved enzymes, identification of active kinases is challenging due to a low abundance of some of these signaling molecules. Although chicken is the first agricultural animal to have a sequenced genome, annotation of the kinome, i.

Modification of the host ubiquitome by bacterial enzymes.

Attachment of ubiquitin molecules to protein substrates is a reversible post-translational modification (PTM), which occurs ubiquitously in eukaryotic cells and controls most cellular processes. As a consequence, ubiquitination is an attractive target of pathogen-encoded virulence factors. Pathogenic bacteria have evolved multiple mechanisms to hijack the host's ubiquitin system to their advantage.

Adolescent rat social play: Amygdalar proteomic and transcriptomic data.

This data article contains the proteomic and transcriptomic data of the amygdala of adolescent rats involved in social play compared to non-behavioural animals. Social play was performed on male Sprague Dawley rats on postnatal day 38 and protein and gene expression in the amygdala was determined following behavioural testing. The protein expression was measured by analysing trypsin digested protein samples using a LTQ Orbitrap Velos mass spectrometer equipped with an Advion nanomate ESI source.

Proteomic and transcriptional profiling of rat amygdala following social play.

Social play is the most characteristic form of social interaction which is necessary for adolescents to develop proper cognitive, emotional, and social competency. The information available on neural substrates and the mechanism involved in social play is limited. This study characterized social play by proteomic and transcriptional profiling studies.

Hectd3 promotes pathogenic Th17 lineage through Stat3 activation and Malt1 signaling in neuroinflammation.

Polyubiquitination promotes proteasomal degradation, or signaling and localization, of targeted proteins. Here we show that the E3 ubiquitin ligase Hectd3 is necessary for pathogenic Th17 cell generation in experimental autoimmune encephalomyelitis (EAE), a mouse model for human multiple sclerosis. Hectd3-deficient mice have lower EAE severity, reduced Th17 program and inefficient Th17 cell differentiation.

PGE2 Augments Inflammasome Activation and M1 Polarization in Macrophages Infected With Typhimurium and .

Eicosanoids are cellular metabolites, which shape the immune response, including inflammatory processes in macrophages. The effects of these lipid mediators on inflammation and bacterial pathogenesis are not clearly understood. Certain eicosanoids are suspected to act as molecular sensors for the recruitment of neutrophils, while others regulate bacterial uptake.

Proteome-wide lysine acetylation identification in developing rice (Oryza sativa) seeds and protein co-modification by acetylation, succinylation, ubiquitination, and phosphorylation.

Protein lysine acetylation is a highly conserved post-translational modification with various biological functions. However, only a limited number of acetylation sites have been reported in plants, especially in cereals, and the function of non-histone protein acetylation is still largely unknown. In this report, we identified 1003 lysine acetylation sites in 692 proteins of developing rice seeds, which greatly extended the number of known acetylated sites in plants.