The gut microbiota plays a significant role in the pathogenesis of inflammatory bowel disease (IBD). However, the role of
infection and
-altered gut microbiota in the development of inflammatory ...diseases and their underlying mechanisms are not well understood.
We investigated the effect of
ST4 and ST7 infection on the intestinal microbiota, metabolism, and host immune responses, and then explored the role of
-altered gut microbiome in the development of dextran sulfate sodium (DSS)-induced colitis in mice.
This study showed that prior colonization with ST4 conferred protection from DSS-induced colitis through elevating the abundance of beneficial bacteria, short-chain fatty acid (SCFA) production and the proportion of Foxp3
and IL-10-producing CD4
T cells. Conversely, prior ST7 infection exacerbated the severity of colitis by increasing the proportion of pathogenic bacteria and inducing pro-inflammatory IL-17A and TNF-α-producing CD4
T cells. Furthermore, transplantation of ST4- and ST7-altered microbiota resulted in similar phenotypes.
Our data showed that ST4 and ST7 infection exert strikingly differential effects on the gut microbiota, and these could influence the susceptibility to colitis. ST4 colonization prevented DSS-induced colitis in mice and may be considered as a novel therapeutic strategy against immunological diseases in the future, while ST7 infection is a potential risk factor for the development of experimentally induced colitis that warrants attention.
Background: Recent studies revealed the role of the PAC1 (ADCYAP1R1) gene variability in vulnerability to posttraumatic stress disorder in women. Due to the relatively high comorbidity of ...posttraumatic stress disorder and substance use disorder, we hypothesized about possible associations between PAC1 gene and problematic alcohol use. Method: The sample studied consisted of 491 women aged 18-28 years (mean age =21.76 years; SD =1.83) and the Alcohol Use Disorders Identification Test was used to assess drinking problems. We successfully genotyped 17 single-nucleotide polymorphisms in the PAC1 gene. Results: Single locus analysis revealed a significant (after correction for multiple testing) association between intronic polymorphism rs2302475 and problematic alcohol use (P=0.00048; recessive model). This result was strengthened by the haplotype analysis (P=0.00379). Conclusion: Our results suggest that the PACAP/PAC1 signaling system is implicated in the development of problematic alcohol use in women. Keywords: problematic alcohol use, PAC1 gene, AUDIT, HPA axis
The role of the T-cell receptor (TCR) in commitment of thymocytes to regulatory CD4(+)Foxp3(+) and conventional CD4(+)Foxp3(-) T-cell lineages remains controversial. According to the prevailing view, ...commitment to the former lineage, in contrast to the latter, requires that high affinity TCRs bind rare class II MHC/peptide complexes presented in 'thymic niches', which could explain differences between their TCR repertoires. Here we challenge this view and show that the binding of identical TCRs to the same ubiquitously expressed MHC/peptide complex often directs thymocytes to both CD4(+) lineages, indicating that the TCR affinity does not play the instructive role, and that restricted presentation of peptides in 'thymic niches' is not necessary for selection of CD4(+)Foxp3(+) T cells. However, depending on whether immature thymocytes bound the ligand predominantly with low or high affinity, the repertoires of regulatory and conventional CD4(+) T cells were correspondingly similar or mostly different, suggesting that negative rather than positive selection sets them apart.
Insane Run Tomasik, Wojciech
2020, 2020-08-25, Letnik:
14
eBook
Odprti dostop
This is a book about impending catastrophe. The metaphorical insane “run“ ends with the outbreak of the First World War. The book focuses on European culture of the late nineteenth century and the ...Polish contribution to it. The word “dark“ used to describe modernity is understood as a metaphor of gradual and permanent devaluation of the idea of progress, as a fading hope for the future of Europe as bright, predictable, prosperous, and safe. The “darkening“ also receives a literal sense. At the end of the nineteenth century, darkness found its way back to the public space – in the theaters, panoramas, dioramas, and “love tunnels“, which awaited the visitors of American and European amusement parks.
A good correlation between the expression of mucin1 (MUC1) and T antigen was found in breast cancer tumors and breast cancer cell lines, especially after treatment with neuraminidase. The association ...between the appearance of T antigen and the overexpression of MUC1 was further confirmed by transfecting MDA-MB-231 cells and murine 4T1 mammary carcinoma cells with cDNA for MUC1 and using an RNAi approach to inhibit the expression of MUC1 gene in T47D cells. Furthermore, we discovered that in 4T1 cells which express the sialyl Le(X) antigen, overexpression of MUC1 caused not only appearance of T antigen, but also loss of the sialyl Le(X) structure. As the observed changes in O-glycan synthesis can be associated with changes in the expression of specific glycosyltransferases, core 1 β1,3-galactosyltransferase, core 2 β1,6-N-acetylglucosaminyltransferase (C2GnT1) and β-galactoside α2,3-sialyltransferase (ST3Gal I), we studied their expression in parental, vector-transfected and MUC1-transfected MDA-MB-231 and 4T1 cells as well as T47D cells transduced with small hairpin RNA targeted MUC1 mRNA. It was found that the expression of C2GnT1 and ST3Gal I is highly decreased in MUC1-expressing MDA-MB-231 and 4T1 cells and increased in T47D cells with suppressed expression of MUC1. Therefore, we found that changes in the structure of O-linked oligosaccharides, resulting in the occurrence of T antigen, are at least partially associated with MUC1 overexpression which down-regulates the expression of C2GnT1 and ST3Gal I. We showed also that the overexpression of MUC1 in 4T1 cells changes their adhesive properties, as MUC1-expressing cells do not adhere to E-selectin, but bind galectin-3.
Themis is important in regulating positive selection of thymocytes during T cell development, but its role in peripheral T cells is less understood. Here, we investigated T cell activation and its ...sequelae using a tamoxifen-mediated, acute Themis deletion mouse model. We find that proliferation, effector functions including anti-tumor killing, and up-regulation of energy metabolism are severely compromised. This study reveals the phenomenon of peripheral adaptation to loss of Themis, by demonstrating direct TCR-induced defects after acute deletion of Themis that were not evident in peripheral T cells chronically deprived of Themis in dLck-Cre deletion model. Peripheral adaptation to long-term loss was compared using chronic versus acute tamoxifen-mediated deletion and with the (chronic) dLck-Cre deletion model. We found that upon chronic tamoxifen-mediated Themis deletion, there was modulation in the gene expression profile for both TCR and cytokine signaling pathways. This profile overlapped with (chronic) dLck-Cre deletion model. Hence, we found that peripheral adaptation induced changes to both TCR and cytokine signaling modules. Our data highlight the importance of Themis in the activation of CD8
+
T cells.
Helios transcription factor and semaphorin receptor Nrp-1 were originally described as constitutively expressed at high levels on CD4+Foxp3+ T regulatory cells of intrathymic origin (tTregs). On the ...other hand, CD4+Foxp3+ Tregs generated in the periphery (pTregs) or induced ex vivo (iTregs) were reported to express low levels of Helios and Nrp-1. Soon afterwards the reliability of Nrp-1 and Helios as markers discriminating between tTregs and pTregs was questioned and until now no consensus has been reached. Here, we used several genetically modified mouse strains that favor pTregs or tTregs formation and analyzed the TCR repertoire of these cells. We found that Tregs with variable levels of Nrp-1 and Helios were abundant in mice with compromised ability to support natural differentiation of tTregs or pTregs. We also report that TCR repertoires of Treg clones expressing high or low levels of Nrp-1 or Helios are similar and more alike repertoire of CD4+Foxp3+ than repertoire of CD4+Foxp3- thymocytes. These results show that high vs. low expression of Nrp-1 or Helios does not unequivocally identify Treg clones of thymic or peripheral origin.
Research on the processing of sexual stimuli has proved that such material has high priority in human cognition. Yet, although sex differences in response to sexual stimuli were extensively discussed ...in the literature, sexual orientation was given relatively little consideration, and material suitable for relevant research is difficult to come by. With this in mind, we present a collection of 200 erotic images, accompanied by their self-report ratings of emotional valence and arousal by homo- and heterosexual males and females (n = 80, divided into four equal-sized subsamples). The collection complements the Nencki Affective Picture System (NAPS) and is intended to be used as stimulus material in experimental research. The erotic images are divided into five categories, depending on their content: opposite-sex couple (50), male couple (50), female couple (50), male (25) and female (25). Additional 100 control images from the NAPS depicting people in a non-erotic context were also used in the study. We showed that recipient sex and sexual orientation strongly influenced the evaluation of erotic content. Thus, comparisons of valence and arousal ratings in different subject groups will help researchers select stimuli set for the purpose of various experimental designs. To facilitate the use of the dataset, we provide an on-line tool, which allows the user to browse the images interactively and select proper stimuli on the basis of several parameters. The NAPS ERO image collection together with the data are available to the scientific community for non-commercial use at http://naps.nencki.gov.pl.
148 enterococcal strains: E.faecalis (108), E.faecium (35), E.gallinarum (3), E.casseliflavus (1) and E.durans (1) from various clinical specimens were investigated for their ability to adhere to ...Caco-2 and HEp-2 cell lines, and also for the presence of the esp gene, biofilm formation, production of haemolysins, DNAse and lipase. Several types of enterococcal adhesion to both cell lines were noted. An aggregative adherence was the most frequent among E.faecalis and E.faecium isolates. Other species presented various adhesive types. The occurrence of virulence factors in the whole group of strains was as follows: esp gene in 53.4%, biofilm in 45.3%, haemolysins in 15.5%, DNAse in 12.2% and lipase in 33.1% of enterococcal isolates. It appears that the adherence of the enterococci studied was not significantly associated with the presence of virulence factors.
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