11 research outputs found

    Accelerated retinal aging in PACAP knock-out mice

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    Pituitary adenylate cyclase activating polypeptide (PACAP) is a neurotrophic and neuroprotective peptide. PACAP and its receptors are widely distributed in the retina. A number of reports provided evidence that PACAP is neuroprotective in retinal degenerations. The current study compared retina cell type-specific differences in young (3-4months) and aged adults (14-16months), of wild-type (WT) mice and knock-out (KO) mice lacking endogenous PACAP production during the course of aging. Histological, immunocytochemical and Western blot examinations were performed. The staining for standard neurochemical markers (tyrosine hydroxylase for dopaminergic cells, calbindin 28 kDa for horizontal cells, protein kinase Calpha for rod bipolar cells) of young adult PACAP KO retinas showed no substantial alterations compared to young adult WT retinas, except for the specific PACAP receptor (PAC1-R) staining. We could not detect PAC1-R immunoreactivity in bipolar and horizontal cells in young adult PACAP KO animals. Some other age-related changes were observed only in the PACAP KO mice only. These alterations included horizontal and rod bipolar cell dendritic sprouting into the photoreceptor layer and decreased ganglion cell number. Also, Muller glial cells showed elevated GFAP expression compared to the aging WT retinas. Furthermore, Western blot analyses revealed significant differences between the phosphorylation state of ERK1/2 and JNK in KO mice, indicating alterations in the MAPK signaling pathway. These results support the conclusion that endogenous PACAP contributes to protection against aging of the nervous system

    Ecological divergence of Chaetopteryx rugulosa species complex (Insecta, Trichoptera) linked to climatic niche diversification

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    Climate is often considered to be an important, but indirect driver of speciation. Indeed, environmental factors may contribute to the formation of biodiversity, but to date this crucial relationship remains largely unexplored. Here we investigate the possible role of climate, geological factors, and biogeographical processes in the formation of a freshwater insect species group, the Chaetopteryx rugulosa species complex (Trichoptera) in the Western Balkans. We used multi-locus DNA sequence data to establish a dated phylogenetic hypothesis for the group. The comparison of the dated phylogeny with the geological history of the Western Balkans shows that lineage formation coincided with major past Earth surface and climatic events in the region. By reconstructing present-day habitat conditions (climate, bedrock geology), we show that the lineages of C. rugulosa species complex have distinct climatic but not bedrock geological niches. Without exception, all splits associated with Pliocene/Pleistocene transition led to independent, parallel split into ‘warm’ and ‘cold’ sister lineages. This indicates a non-random diversification on the C. rugulosa species complex associated with late Pliocene climate in the region. We interpreted the results as the diversification of the species complex were mainly driven by ecological diversification linked to past climate change, along with geographical isolation

    Expression and estrogen-dependent up-regulation of Transient Receptor Potential Ankyrin 1 (TRPA1) and Vanilloid 1 (TRPV1) ion channels in the rat endometrium

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    Transient Receptor Potential Ankyrin 1 (TRPA1) and Vanilloid 1 (TRPV1) cation channels localized predominantly on capsaicin-sensitive peptidergic sensory nerves play essential roles in pain, hyperalgesia and neurogenic inflammation. They are activated by a variety of noxious stimuli, chemical irritants and cold or heat, respectively. Besides sensory nerves, both receptors have been described on epithelial and immune cells. Estrogen-induced TRPV1 up-regulation in the human uterus suggests its potential involvement in pain during the reproductive cycle. Since there are no data regarding TRPA1 expression in the endometrium and little is known about TRPV1 regulation, we investigated estrogen- and progesterone-dependent alterations of these channels in the rat endometrium. Different groups of sexually premature 4-week-old and adult 4-month-old female rats were treated with subcutaneously implanted wax pellets containing synthetic estrogen analog diethylstilbestrol (DES, 100 µg), progesterone (4 mg) and their combination for 8 or 12 days, respectively. Ovariectomy was performed in separate groups of 4-month-old animals (n=5/group). TRPA1 and TRPV1 mRNA levels were measured in the endometrium layer with quantitative PCR, while the localization of the receptor proteins was determined with immunohistochemistry on paraffin-embedded uterus sections. Both TRPA1 and TRPV1 were detected in the rat endometrium at mRNA and protein levels as well, showing their remarkable local, non-neuronal expression. DES treatment resulted in a 5-fold and 7-fold significant up-regulation of TRPV1 mRNA in young and adult rats, respectively, which were absent if progesterone was added simultaneously. DES also induced significant elevation of TRPA1 mRNA in both groups. Progesterone by itself did not alter the levels of either channel in either group. In young rats, weak TRPV1 and A1 staining were observed in the epithelium, while in adult animals it was detected in the stroma and the glands with weak expression in the epithelium. Further investigations are in process to elucidate the functions of TRPA1 and TRPV1 in conditions related to pain and inflammation. SROP-4.2.2.A-11/1/KONV-2012-002

    Biofilm Eradication by Symmetrical Selenoesters for Food-Borne Pathogens

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    © 2020 by the authors.Infections caused by Salmonella species and Staphylococcus aureus represent major health and food industry problems. Bacteria have developed many strategies to resist the antibacterial activity of antibiotics, leading to multidrug resistance (MDR). The over-expression of drug efflux pumps and the formation of biofilms based on quorum sensing (QS) can contribute the emergence of MDR. For this reason, the development of novel effective compounds to overcome resistance is urgently needed. This study focused on the antibacterial activity of nine symmetrical selenoesters (Se-esters) containing additional functional groups including oxygen esters, ketones, and nitriles against Gram-positive and Gram-negative bacteria. Firstly, the minimum inhibitory concentrations of the compounds were determined. Secondly, the interaction of compounds with reference antibiotics was examined. The efflux pump (EP) inhibitory properties of the compounds were assessed using real-time fluorimetry. Finally, the anti-biofilm and quorum sensing inhibiting effects of selenocompounds were determined. The methylketone and methyloxycarbonyl selenoesters were the more effective antibacterials compared to cyano selenoesters. The methyloxycarbonyl selenoesters (Se-E2 and Se-E3) showed significant biofilm and efflux pump inhibition, and a methyloxycarbonyl selenoester (Se-E1) exerted strong QS inhibiting effect. Based on results selenoesters could be promising compounds to overcome bacterial MDR.The study was supported by the projects SZTE ÁOK-KKA 2018/270-62-2 of the University of Szeged, Faculty of Medicine and GINOP-2.3.2-15-2016-00038 (Hungary). M.N. was supported by EFOP 3.6.3-VEKOP-16-2017-00009. E.D-A. was supported by ‘Iniciativas Ropelanas’ and ‘Asociación Cultural Trevinca’, two associations from Zamora (Spain), that promote cancer research.Peer reviewe
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