Activation of Enteroendocrine Cells via TLRs Induces Hormone, Chemokine, and Defensin Secretion

Abstract Enteroendocrine cells are known primarily for their production of hormones that affect digestion, but they might also be implicated in sensing and neutralizing or expelling pathogens. We evaluate the expression of TLRs and the response to specific agonists in terms of cytokines, defensins, and hormones in enteroendocrine cells. The mouse enteroendocrine cell line STC-1 and C57BL/6 mice are used for in vitro and in vivo studies, respectively. The presence of TLR4, 5, and 9 is investigated by RT-PCR, Western blot, and immunofluorescence analyses. Activation of these receptors is studied evaluating keratinocyte-derived chemokine, defensins, and cholecystokinin production in response to their specific agonists. In this study, we show that the intestinal enteroendocrine cell line STC-1 expresses TLR4, 5, and 9 and releases cholecystokinin upon stimulation with the respective receptor agonists LPS, flagellin, and CpG-containing oligodeoxynucleotides. Release of keratinocyte-derived chemokine and β-defensin 2 was also observed after stimulation of STC-1 cells with the three TLR agonists, but not with fatty acids. Consistent with these in vitro data, mice showed increased serum cholecystokinin levels after oral challenge with LPS, flagellin, or CpG oligodeoxynucleotides. In addition to their response to food stimuli, enteroendocrine cells sense the presence of bacterial Ags through TLRs and are involved in neutralizing intestinal bacteria by releasing chemokines and defensins, and maybe in removing them by releasing hormones such as cholecystokinin, which induces contraction of the muscular tunica, favoring the emptying of the distal small intestine

L'Universit\ue0 si apre ai non studenti: un progetto di partecipazione e apprendimenti per giovani con disabilit\ue0 intellettiva in una Universit\ue0 italiana

Il contributo pone al centro della riflessione il tema della formazione post-secondaria per giovani con disabilit\ue0 intellettiva, documentando un innovativo progetto pilota che ha sostenuto la partecipazione e gli apprendimenti di giovani con disabilit\ue0 intellettiva in una Universit\ue0 italiana. Lo studio affronta alcuni nodi cruciali relativi ai processi di accompagnamento verso l\u2019adultit\ue0 di giovani con disabilit\ue0 intellettiva sulla base di un quadro teorico e normativo di riferimento, la documentazione rigorosa del progetto attraverso interviste rivolte a testimoni privilegiati e un approfondimento sulle scelte organizzative e didattiche intraprese. L\u2019esperienza presentata vuole essere un'occasione di riflessione sulle forme attraverso cui anche l\u2019Universit\ue0 pu\uf2 diventare agente di cambiamento nel sostenere i processi inclusivi, come gi\ue0 in diversi paesi sta accadendo

L’Università si apre ai non studenti: un progetto di partecipazione e di apprendimenti per giovani con disabilità intellettiva in una Università italiana

This paper aims to set at the center of consideration post-secondary education for young peoplewith intellectual disabilities. It deals with documentation about an innovative pilot project thatsupported the participation and learning of young people with intellectual disabilities in an ItalianUniversity. The study faces some crucial issues related to the accompanying processes towardsadulthood of young people with intellectual disabilities. The investigation employs a theoreticaland regulatory framework, a rigorous documentation through interviews to the actors of theproject and an in-depth analysis on the choices of organizational and didactic activities. Suchexperience is intended to be an opportunity to reflect on the ways the University, as it happenselsewhere, can also be a promoter of change supporting inclusive processes

Misbehaviour of XIST RNA in Breast Cancer Cells

A role of X chromosome inactivation process in the development of breast cancer have been suggested. In particular, the relationship between the breast cancer predisposing gene BRCA1 and XIST, the main mediator of X chromosome inactivation, has been intensely investigated, but still remains controversial. We investigated this topic by assessing XIST behaviour in different groups of breast carcinomas and in a panel of breast cancer cell lines both BRCA1 mutant and wild type. In addition, we evaluated the occurrence of broader defects of heterochromatin in relation to BRCA1 status in breast cancer cells. We provide evidence that in breast cancer cells BRCA1 is involved in XIST regulation on the active X chromosome, but not in its localization as previously suggested, and that XIST can be unusually expressed by an active X and can decorate it. This indicates that the detection of XIST cloud in cancer cell is not synonymous of the presence of an inactive X chromosome. Moreover, we show that global heterochromatin defects observed in breast tumor cells are independent of BRCA1 status. Our observations sheds light on a possible previously uncharacterized mechanism of breast carcinogenesis mediated by XIST misbehaviour, particularly in BRCA1-related cancers. Moreover, the significant higher levels of XIST-RNA detected in BRCA1-associated respect to sporadic basal-like cancers, opens the possibility to use XIST expression as a marker to discriminate between the two groups of tumors

Conditions for the early onset of blisters during heat treatments of Al-Si-Cu CAST PART

The evolution of subsurface pressurized pores, originating blisters during heat treatment cycles, on High Pressure Die Cast components made of Al-Si-Cu alloys was studied using a Finite Element Model in order to understand under which conditions blister form even below 400°C. The initial defect geometry, depth, inner pressure and the maximum temperature of the thermal cycle were varied in limited ranges, while the material was modelled as elastoplastic, considering creep effects negligible. Results suggested that blisters develop as a result of high plastic strain accumulation in localized regions lying between the pore and the outer surface and that blisters can form even at temperatures of 350-370°C. The simulations were experimentally validated by two sets of experiments carried out on cast parts, monitoring the surface and volume evolution of subsurface defects coupled by optical microscopy and microtomography analyses