Inhibition of protein translation as a novel mechanism for prostaglandin E2 regulation of cell functions

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154239/1/fsb2028001008.pd

Semi- and fully synthetic carbohydrate vaccines against pathogenic bacteria : recent developments

The importance of vaccine-induced protection was repeatedly demonstrated over the last three decades and emphasized during the recent COVID-19 pandemic as the safest and most effective way of preventing infectious diseases. Vaccines have controlled, and in some cases, eradicated global viral and bacterial infections with high efficiency and at a relatively low cost. Carbohydrates form the capsular sugar coat that surrounds the outer surface of human pathogenic bacteria. Specific surface-exposed bacterial carbohydrates serve as potent vaccine targets that broadened our toolbox against bacterial infections. Since first approved for commercial use, antibacterial carbohydrate-based vaccines mostly rely on inherently complex and heterogenous naturally derived polysaccharides, challenging to obtain in a pure, safe, and cost-effective manner. The introduction of synthetic fragments identical with bacterial capsular polysaccharides provided well-defined and homogenous structures that resolved many challenges of purified polysaccharides. The success of semisynthetic glycoconjugate vaccines against bacterial infections, now in different phases of clinical trials, opened up new possibilities and encouraged further development towards fully synthetic antibacterial vaccine solutions. In this mini-review, we describe the recent achievements in semi- and fully synthetic carbohydrate vaccines against a range of human pathogenic bacteria, focusing on preclinical and clinical studies

Protein kinase A inhibition of macrophage maturation is accompanied by an increase in DNA methylation of the colonyâ stimulating factor 1 receptor gene

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134212/1/imm12641.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134212/2/imm12641_am.pd

Nicotinic receptors on rat alveolar macrophages dampen ATP-induced increase in cytosolic calcium concentration

Background: Nicotinic acetylcholine receptors (nAChR) have been identified on a variety of cells of the immune system and are generally considered to trigger anti-inflammatory events. In the present study, we determine the nAChR inventory of rat alveolar macrophages (AM), and investigate the cellular events evoked by stimulation with nicotine. Methods: Rat AM were isolated freshly by bronchoalveolar lavage. The expression of nAChR subunits was analyzed by RT-PCR, immunohistochemistry, and Western blotting. To evaluate function of nAChR subunits, electrophysiological recordings and measurements of intracellular calcium concentration ([Ca2+]i) were conducted. Results: Positive RT-PCR results were obtained for nAChR subunits α3, α5, α9, α10, β1, and β2, with most stable expression being noted for subunits α9, α10, β1, and β2. Notably, mRNA coding for subunit α7 which is proposed to convey the nicotinic anti-inflammatory response of macrophages from other sources than the lung was not detected. RT-PCR data were supported by immunohistochemistry on AM isolated by lavage, as well as in lung tissue sections and by Western blotting. Neither whole-cell patch clamp recordings nor measurements of [Ca2+]i revealed changes in membrane current in response to ACh and in [Ca2+]i in response to nicotine, respectively. However, nicotine (100 μM), given 2 min prior to ATP, significantly reduced the ATP-induced rise in [Ca2+]i by 30%. This effect was blocked by α-bungarotoxin and did not depend on the presence of extracellular calcium. Conclusions: Rat AM are equipped with modulatory nAChR with properties distinct from ionotropic nAChR mediating synaptic transmission in the nervous system. Their stimulation with nicotine dampens ATP-induced Ca2+-release from intracellular stores. Thus, the present study identifies the first acute receptor-mediated nicotinic effect on AM with anti-inflammatory potential

Eicosanoid control over antigen presenting cells in asthma

Asthma is a common lung disease affecting 300 million people worldwide. Allergic asthma is recognized as a prototypical Th2 disorder, orchestrated by an aberrant adaptive CD4+ T helper (Th2/Th17) cell immune response against airborne allergens, that leads to eosinophilic inflammation, reversible bronchoconstriction, and mucus overproduction. Other forms of asthma are controlled by an eosinophil-rich innate ILC2 response driven by epithelial damage, whereas in some patients with more neutrophilia, the disease is driven by Th17 cells. Dendritic cells (DCs) and macrophages are crucial regulators of type 2 immunity in asthma. Numerous lipid mediators including the eicosanoids prostaglandins and leukotrienes influence key functions of these cells, leading to either pro- or anti-inflammatory effects on disease outcome. In this review, we will discuss how eicosanoids affect the functions of DCs and macrophages in the asthmatic lung and how this leads to aberrant T cell differentiation that causes disease

Metabolism-driven glycosylation represents therapeutic opportunities in interstitial lung diseases

Metabolic changes are coupled with alteration in protein glycosylation. In this review, we will focus on macrophages that are pivotal in the pathogenesis of pulmonary fibrosis and sarcoidosis and thanks to their adaptable metabolism are an attractive therapeutic target. Examples presented in this review demonstrate that protein glycosylation regulates metabolism-driven immune responses in macrophages, with implications for fibrotic processes and granuloma formation. Targeting proteins that regulate glycosylation, such as fucosyltransferases, neuraminidase 1 and chitinase 1 could effectively block immunometabolic changes driving inflammation and fibrosis, providing novel avenues for therapeutic interventions

APPLICATION OF CLASSIFICATION TREES TO ANALYSE POKER GAME OUTCOME

Niniejsza publikacja stanowi próbę scharakteryzowania deterministycznych czynników wpływających na wygraną w pokera. Przeprowadzono analizę w oparciu o jedną z metod eksploracji danych – drzewa klasyfikacyjne. Wybór tej techniki podyktowany był wykorzystaniem danych jakościowych jako zmiennych objaśniających rozgrywkę pokerową oraz prostotą prezentacji otrzymanych wyników, nawet przy bardzo rozbudowanych drzewach. W badaniu odkryto kilka czynników, które w istotny sposób mają wpływ na przebieg gry.The paper aims to characterize key factors determining poker game outcome. The analysis was based on classification trees and this was due to the qualitative data used as the explanatory variables. The method enables clear presentation of the results even in case of very complex tree structures. The study describes also a few other factors that significantly influence the game outcome

Microbiological production of protein with β-glucanase activity

W pracy przedstawiono produkcję enzymu degradującego niektóre rodzaje hemicelulozy. Białko zostało wyprodukowane przez zmodyfikowany genetycznie szczep E. coli w reaktorze mikrobiologicznym. Wskazano optymalne warunki prowadzenia procesu biosyntezy białka. Wyznaczono stałą szybkości reakcji preparatu oczyszczonego. Określono stabilność operacyjną enzymu będącą kluczowym parametrem dla potencjalnego zastosowania w procesie wielkotonażowym hydrolizy komponentów biomasy roślinnej.The paper presents production of enzyme which degrades some hemicellulose form. The protein was produced by a genetically modified strain of E. coli in the microbiological reactor. The optimal conditions for protein biosynthesis process were indicated. The reaction rate constant was determined for the purified preparation. The enzyme stability was evaluated as a crucial operational parameter for potential application in the hydrolysis of plant biomass components in a large-tonnage process