Snedkerwaller9796

Childhood and adolescence represent a time notable for the emergence of many psychiatric disorders, where comorbidity and co-occurrence of symptoms are well-documented. However, it remains unclear whether there exists common brain structural disturbance across psychiatric disorders in youth. Here, we conduct a transdiagnostic meta-analysis of 132 structural neuroimaging experiments in youth consisting of multiple psychiatric diagnoses. Compared to healthy peers, youth psychiatric disorders are characterized by reduced grey matter volume (GMV) of amygdala and lateral orbitofrontal cortex and enhanced GMV of ventromedial prefrontal cortex and precuneus. These four regions were then subjected to functional connectivity and decoding analyses based on healthy participant datasets, allowing for a data-driven quantitative inference on psychophysiological functions. These regions and their networks mapped onto systems implicated in negative valence, positive valence, as well as social and cognitive functioning. Together, our findings are consistent with transdiagnostic models of psychopathology, uncovering common structural disturbance across youth psychiatric disorders, potentially reflecting an intermediate transdiagnostic phenotype in association with broad dimensions of youth psychopathology.Background Beta-lactoglobulin (BLG) is a bovine lipocalin in milk with innate defense function. It is not understood under which circumstances BLG is associated with tolerance or allergy towards milk. Objective Here we assessed the capacity of ligand-free (apo-) versus -loaded (holo-) BLG to protect mice against allergy using iron-quercetin as exemplary ligand, and studied the molecular mechanisms. Methods Binding of iron-quercetin into BLG was modeled and confirmed by spectroscopy and docking calculations. Serum IgE binding of milk allergic and tolerant children to apo- and holo-BLG was assessed. Mice were intranasally treated with apo- versus holo-BLG and after systemic challenge immunologically analysed. AhR activation was evaluated with reporter cells and Cyp1A1 expression. Treated human peripheral blood mononuclear cells and human mast cells were assessed by FACS and degranulation, respectively. Results Modelling predicted masking of major IgE and T cell epitopes of BLG by ligand-binding. In line, IgE binding of milk allergic children was reduced towards holo-BLG which also impaired degranulation of mast cells. In mice, only treatments with holo-BLG prevented allergic sensitization and anaphylaxis, while sustaining regulatory T cells. BLG facilitated quercetin-dependent AhR-activation and, downstream AhR, lung Cyp1A1 expression. Holo-BLG shuttled iron into monocytic cells and impaired their antigen-presentation. Conclusion The cargo of holo-BLG is decisive in preventing allergy in vivo. BLG without cargo acted as allergen in vivo and further primed human mast cells for degranulation in an antigen-independent fashion. Our data provide mechanistic explanation why the same proteins can either act as tolerogen or allergen.Background IgG4-related disease (IgG4-RD) is an immune-mediated fibrotic disorder that has been linked to CD4+ cytotoxic T lymphocytes (CD4+CTLs). The effector phenotype of CD4+CTLs, the relevance of both CD8+ cytotoxic T lymphocytes (CD8+CTLs) and of apoptotic cell death remain undefined in IgG4-RD. Objective The goals of this study were to define CD4+CTL heterogeneity, characterize the CD8+CTL response in the blood and in lesions, and determine whether enhanced apoptosis may contribute to the pathogenesis of IgG4-RD. Methods Blood analyses were undertaken using flow cytometry, cell sorting, transcriptomic analyses at the population and single cell levels and next generation sequencing for the TCR repertoire. Tissues were interrogated using multi-color immunofluorescence. Results were correlated with clinical data. Results We establish that among circulating CD4+CTLs in IgG4-RD, CD27loCD28loCD57hi cells are the dominant effector subset, exhibit marked clonal-expansion and differentially express genes relevant to cytotoxicity, activation and enhanced metabolism. We also observed prominent infiltration of granzyme A-expressing CD8+CTLs in disease tissues and clonal-expansion in the blood of effector/memory CD8+ T cells with an activated and cytotoxic phenotype. Tissue studies revealed an abundance of cells undergoing apoptotic cell death disproportionately involving non-immune, non-endothelial cells of mesenchymal origin. Apoptotic cells showed significant upregulation of HLA-DR. Conclusion CD4+CTLs and CD8+CTLs may induce apoptotic cell death in tissues of patients with IgG4-RD with preferential targeting of non-endothelial, non-immune cells of mesenchymal origin. Clinical implication T cell mediated apoptosis in disease lesions may contribute to the induction of fibrosis in IgG4-RD. Effector CD4+CTLs and CD8+CTLs correlate with disease severity in IgG4-RD.Objective The aim of this study was to investigate the effects of two radiopaque agents, barium sulfate (BaSO4) or zirconium oxide (ZrO2) in double antibiotic paste (DAP), on the proliferation and mineral deposition of human dental pulp stem cells (DPSC). Materials and methods Radiopaque antimicrobial medicaments composed of methylcellulose (MC) thickening polymer with BaSO4 or ZrO2 and either 1 or 5 mg/mL DAP (equal portions of metronidazole and ciprofloxacin) were used to investigate DPSC proliferation after 3 days, and alkaline phosphatase (ALP) activity and mineral deposition after 7 and 14 days. Radiopaque agents without DAP and Ca(OH)2 were used as controls. Results MC-BaSO4 DAP and MC-ZrO2 DAP at 1 or 5 mg/mL had no adverse effect on DPSC proliferation, compared to the media and MC controls. MC-ZrO2 (DAP-free) greatly increased ALP activity after 7 days. DPSC mineral deposition was modestly reduced at 7 days by MC-BaSO4 DAP and MC-ZrO2 DAP, but not by DAP-free radiopaque agents, and was most reduced by 5 mg/mL DAP in the 14-day cultures. Conclusions MC-BaSO4 or MC-ZrO2 medicaments containing up to 5 mg/mL of DAP supported the proliferation and early osteogenic differentiation of DPSC. Low DAP concentrations and short culture times led to more favorable effects on ALP activity and mineral deposition by DPSC. The findings suggest that radiopaque agents added for the purpose of detecting whether medicaments occupy the full extent of the root canal may have clinical applications. Radiopaque antibiotic medicaments containing low DAP concentrations may be an alternative to Ca(OH)2 for regenerative endodontic procedures.This study presents the first complete mitochondrial genome (mitogenome) of Caecobarbus geertsii, the Congo blind barb, a cave-dwelling, CITES-protected, cyprinid fish endemic to the Lower Congo basin (DRC). The length of the circular mitogenome is 16,565 base pairs. The 13 protein coding genes, 2 ribosomal RNA genes and 22 transfer RNA genes are similar in position and direction to those of other members of the family Cyprinidae. Phylogenetic analyses including 28 complete mitogenomes from representatives of the subfamily Smiliogastrinae (Cyprinidae), showed that Caecobarbus was nested within a clade including representatives of the genus Enteromius. The data presented in this study provide information on the molecular identification and classification of this threatened species. The results further suggest the need for a taxonomic revision of the genus Enteromius.Sago pith cellulose nanofibril (SPCNF) aerogel derived from sago pith waste (SPW) was successfully produced through three consecutive steps, namely dewaxing and delignification, ultra-sonication and homogenization and freeze drying. The aerogel was characterized using field emission scanning electron microscopy (FE-SEM), Fourier-transform infra-red spectroscopy (FTIR), X-ray diffraction (XRD) and thermogravimetric analysis (TGA). Results of the analyses collectively showed that lignin & hemicellulose were absent in the SPCNF aerogel product which has a high crystallinity index of 88%. The diameters of individual nanofibril constituents of the SPCNF were between 15 and 30 nm and aspect ratios >1000 were observed. The SPCNF aerogel, with a density measured at 2.1 mg/cm3, was efficient in methylene blue (MB) removal with a maximum MB adsorption of 222.2 mg/g at 20 °C. The adsorption of MB onto the SPCNF aerogel was rapid and found to follow a pseudo-second-order kinetic model with the adsorption isotherm being in congruence with the Langmuir model. The SPCNF aerogel exhibited outstanding MB removal efficacies with 5 mg and 20 mg of SPCNF capable of removing over 90% and almost 99% MB, respectively. The optimized pH value and temperature for MB adsorption were determined as pH 7 and 20 °C.The ultrasonic-assisted alkali extraction of Typha domingensis stem polysaccharide (TDSPs) was studied using the response surface methodology. The optimal parameters of TDSPs with maximum yields (12.24± 0.08%) were as follows extraction time 40 min, NaOH concentration 1.5 M and the ratio of water to raw material 25mL/g. The experimental purity of TDSPs was 86.01 ± 0.02. Mineral elements were determined by ICP-AES. The gel permeation chromatography results indicated that TDSPs was a polysaccharide polymer with two peaks with molecular weights of 3182.6 Da (P1) and 3,076,900 Da (P2). The TDSPs consisted of arabinose, rhamnose, galactose, xylose, glucose, mannose, and fructose. The results of NMR and FT-IR spectra represented the presence of β-configurations in TDSPs. Moreover, the TDSPs improved the stimulating effect on the growth of selective probiotic bacteria and showed relatively good antioxidant activity. Therefore, due to its good prebiotic and antioxidant activity, TDSPs could be exploited as a novel natural component in functional food industries.Serotonin (5-HT) receptors have been shown to homodimerize and heterodimerize with other G protein-coupled receptors (GPCRs), although the details of this process have not yet been elucidated. Here we use coarse-grained molecular dynamics on monomeric 5-HT2C receptors to predict the transmembrane (TM) helices involved in such associations. Bcl-2 inhibitor All these simulations were carried out both in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid bilayers and in mixed composition POPC-Cholesterol ones, to show whether the presence of cholesterol could directly influence and drive the dimeric association. The goal is to get insights on the self-assembly pathway leading to GPCRs 5-HT2C oligomerization, which is supposed to be the basis of its constitutional activity. From the analysis of the molecular dynamics trajectories, we observed the formation of 5-HT2C oligomers through self-assembly and we identified the main domains involved in the receptor dimerization. In particular, dimers and oligomers from the two different environments show TM4-TM5 and TM1-TM7-H8 as the preferential dimerization interfaces. Nevertheless, substantial differences arise for oligomers in POPC and in POPC-Chol membranes in POPC-Chol the variability of dimers interfaces is strictly limited to the TM1-TM7-H8 and TM4-TM5 interfaces and the dimorphism depends on cholesterol that directly participates in its formation. These results are in agreement with both experimental evidences and other computational studies conducted on other GPCRs oligomerization.