Secretin attenuates the hereditary repetitive hyperactive movements in a mouse model

It was previously demonstrated that secretin influenced the behavior of rats investigated by open-field test. In the present experiment, we have compared the effect of intracerebroventricular administration of 2 mug of secretin on the behavior of CFLP white and Japanese waltzing mice. These latter animals exhibit stereotypic circular movements. The effect of secretin on the horizontal (ambulation) and vertical movements (rearing and jumping) was investigated in open-field test. The ambulation time and distance were shorter, and the number of rearing and jumping were much lower in Japanese waltzing mice than in CFLP white mice during 30 min-experimental period. In white mice, 2 mug of secretin had no effect on the above-mentioned parameters; however, in Japanese waltzing mice, secretin enhanced the ambulation time and distance to the level of CFLP white mice, but did not influence the rearing and jumping. On the basis of the results, it was concluded that intracerebroventricularly administered secretin attenuated the stereotypic (circulating) movement and improved the horizontal movement indicated by the normalization of the ambulation time and distance; however, it did not influence the explorative behavior (rearing and jumping) in our special animal model

Self-mediated positive selection of T cells sets an obstacle to the recognition of nonself

Adaptive immune recognition is mediated by the binding of peptide–human leukocyte antigen complexes by T cells. Positive selection of T cells in the thymus is a fundamental step in the generation of a responding T cell repertoire: only those T cells survive that recognize human peptides presented on the surface of cortical thymic epithelial cells. We propose that while this step is essential for optimal immune function, the process results in a defective T cell repertoire because it is mediated by self-peptides. To test our hypothesis, we focused on amino acid motifs of peptides in contact with T cell receptors. We found that motifs rarely or not found in the human proteome are unlikely to be recognized by the immune system just like the ones that are not expressed in cortical thymic epithelial cells or not presented on their surface. Peptides carrying such motifs were especially dissimilar to human proteins. Importantly, we present our main findings on two independent T cell activation datasets and directly demonstrate the absence of naïve T cells in the repertoire of healthy individuals. We also show that T cell cross-reactivity is unable to compensate for the absence of positively selected T cells. Additionally, we show that the proposed mechanism could influence the risk for different infectious diseases. In sum, our results suggest a side effect of T cell positive selection, which could explain the nonresponsiveness to many nonself peptides and could improve the understanding of adaptive immune recognition

Pathogen diversity drives the evolution of generalist MHC-II alleles in human populations

Whereas specialist major histocompatibility complex (MHC) molecules initiate immune response against only relatively few pathogens, generalists provide protection against a broad range. Accordingly, this study shows that the geographical distribution of generalist MHC alleles in human populations reflects exposure to diverse infectious diseases

Bőrbetegségek immunpatogenezisének és genetikájának vizsgálata

A szegedi Bőrgyógyászati és Allergológiai Klinikán több évtizede folyik kísérletes bőrgyógyászati kutatás, melynek során számos betegség patogenezisének megismerésében, és új terápiás eljárások kifejlesztésében vettünk részt. Prof. Dr. Dobozy Attila támogatásával klinikánk olyan tudományos műhellyé vált, ami eredményei révén hazai és nemzetközi viszonylatban is jelentős elismertségre tett szert az elmúlt években. Ennek a munkának az egyik fontos állomása az MTA-SZTE Dermatológiai Kutatócsoport megalapítása, ahol a klinikusok kutatókkal együttműködve vesznek részt a kijelölt célok megvalósításában. Az elmúlt évtizedekben a kutatás, oktatás, betegellátás egységének megteremtésével a szegedi Bőrgyógyászati és Allergológiai Klinikán egy szilárd alapokon álló szakmai műhely alakulhatott ki

Comprehensive Proteomic Analysis Reveals Intermediate Stage of Non-Lesional Psoriatic Skin and Points out the Importance of Proteins Outside this Trend

To better understand the pathomechanism of psoriasis, a comparative proteomic analysis was performed with non-lesional and lesional skin from psoriasis patients and skin from healthy individuals. Strikingly, 79.9% of the proteins that were diferentially expressed in lesional and healthy skin exhibited expression levels in non-lesional skin that were within twofold of the levels observed in healthy and lesional skin, suggesting that non-lesional skin represents an intermediate stage. Proteins outside this trend were categorized into three groups: I. proteins in non-lesional skin exhibiting expression similar to lesional skin, which might be predisposing factors (i.e., CSE1L, GART, MYO18A and UGDH); II. proteins that were diferentially expressed in non-lesional and lesional skin but not in healthy and lesional skin, which might be non-lesional characteristic alteration (i.e., CHCHD6, CHMP5, FLOT2, ITGA7, LEMD2, NOP56, PLVAP and RRAS); and III. proteins with contrasting diferential expression in non-lesional and lesional skin compared to healthy skin, which might contribute to maintaining the non-lesional state (i.e., ITGA7, ITGA8, PLVAP, PSAPL1, SMARCA5 and XP32). Finally, proteins diferentially expressed in lesions may indicate increased sensitivity to stimuli, peripheral nervous system alterations, furthermore MYBBP1A and PRKDC were identifed as potential regulators of key pathomechanisms, including stress and immune response, proliferation and diferentiation

The Absence of N-Acetyl-D-glucosamine Causes Attenuation of Virulence of Candida albicans upon Interaction with Vaginal Epithelial Cells In Vitro.

To better understand the molecular events underlying vulvovaginal candidiasis, we established an in vitro system. Immortalized vaginal epithelial cells were infected with live, yeast form C. albicans and C. albicans cultured in the same medium without vaginal epithelial cells were used as control. In both cases a yeast to hyphae transition was robustly induced. Whole transcriptome sequencing was used to identify specific gene expression changes in C. albicans. Numerous genes leading to a yeast to hyphae transition and hyphae specific genes were upregulated in the control hyphae and the hyphae in response to vaginal epithelial cells. Strikingly, the GlcNAc pathway was exclusively triggered by vaginal epithelial cells. Functional analysis in our in vitro system revealed that the GlcNAc biosynthesis is involved in the adherence to, and the ability to kill, vaginal epithelial cells in vitro, thus indicating the key role for this pathway in the virulence of C. albicans upon vulvovaginal candidiasis

Optical Properties, Chemical Composition and the Toxicological Potential of Urban Particulate Matter

This paper discusses the diurnal variation and the interdependences between the physical, chemical and toxicological characteristics of atmospheric carbonaceous particulate matter (CPM) and co-emitted gaseous components. Measurements were carried out at two different urban sites during a 2-month period. On-line measured parameters were optical absorption coefficients (OAC), total number concentration (TNC), mass concentration of CPM and the concentration of gaseous species (CO, NOx and BTEX). Off-line analyses were carried out on filters collected with 6-hour time resolution. The concentrations of elemental carbon (EC), organic carbon (OC), total carbon (TC), levoglucosan (LG) and polycyclic aromatic hydrocarbons (PAH) were determined. The ecotoxicity of CPM was assessed by the Vibrio Fischeri marine bioluminescence inhibition bioassay (ISO 21338:2010). We found (r > 0.498) positive and wavelength dependent correlation between the CPM related parameters based on optical response (OAC, AAE) and thermal stability (TC, EC, OC, OC/TC). We also revealed weak (r = 0.309) or moderate (r = 0.448) correlation between the AAE and the ecotoxicity data indicating that carbonaceous fraction of the ambient particulate matter has ecotoxicological impact. Based on the determined correlations, we propose the applicability of the AAE determined by multi wavelength photoacoustic measurements as a possible candidate for first-screening the toxicological impact of optically active carbonaceous ambient particulate matter. The strengths and the limitations of this methodology are both discussed here