ER Stress-Inducible Factor CHOP Affects the Expression of Hepcidin by Modulating C/EBPalpha Activity

Endoplasmic reticulum (ER) stress induces a complex network of pathways collectively termed the unfolded protein response (UPR). The clarification of these pathways has linked the UPR to the regulation of several physiological processes. However, its crosstalk with cellular iron metabolism remains unclear, which prompted us to examine whether an UPR affects the expression of relevant iron-related genes. For that purpose, the HepG2 cell line was used as model and the UPR was activated by dithiothreitol (DTT) and homocysteine (Hcys). Here, we report that hepcidin, a liver secreted hormone that shepherds iron homeostasis, exhibits a biphasic pattern of expression following UPR activation: its levels decreased in an early stage and increased with the maintenance of the stress response. Furthermore, we show that immediately after stressing the ER, the stress-inducible transcription factor CHOP depletes C/EBPα protein pool, which may in turn impact on the activation of hepcidin transcription. In the later period of the UPR, CHOP levels decreased progressively, enhancing C/EBPα-binding to the hepcidin promoter. In addition, analysis of ferroportin and ferritin H revealed that the transcript levels of these iron-genes are increased by the UPR signaling pathways. Taken together, our findings suggest that the UPR can have a broad impact on the maintenance of cellular iron homeostasis

The disruption of proteostasis in neurodegenerative diseases

Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio

Detecting macroecological patterns in bacterial communities across independent studies of global soils

This study and participants were funded in part by ERC Adv grant 26055290 (KSR, WHvdP); BBSRC David Phillips Fellowship (BB/L02456X/1) (FTDV); ERC Grant Agreements 242658 [BIOCOM] and 647038 [BIODESERT] (FTM); the European Regional Development Fund (Centre of Excellence EcolChange) (JD); Yorkshire Agricultural Society, Nafferton Ecological Farming Group, and the Northumbria University Research Development Fund (CHO); BBSRC Training Grant (BB/K501943/1) (CH); Wallenberg Academy Fellowship (KAW 2012.0152), Formas (214-2011-788) and Vetenskapsrådet (612-2011-5444) (ED); the Glastir Monitoring & Evaluation Programme (Contract reference: C147/2010/11) and the full support of the GMEP team on the Glastir project (DLJ, SC, DAR)

Plasma cell differentiation initiates a limited ER stress response by specifically suppressing the PERK-dependent branch of the unfolded protein response

In response to terminal differentiation signals that enable B cells to produce vast quantities of antibodies, a dramatic expansion of the secretory pathway and a corresponding increase in the molecular chaperones and folding enzymes that aid and monitor immunoglobulin synthesis occurs. Recent studies reveal that the unfolded protein response (UPR), which is normally activated by endoplasmic reticulum (ER) stress, plays a critical role in this process. Although B cells activate all three branches of the UPR in response to pharmacological inducers of the pathway, plasma cell differentiation elicits only a partial UPR in which components of the PKR-like ER kinase (PERK) branch are not expressed. This prompted us to further characterize UPR activation during plasma cell differentiation. We found that in response to lipopolysaccharides (LPS)-induced differentiation of the I.29 μ+ B cell line, Ire1 was activated early, which led to splicing of XBP-1. PERK was partially phosphorylated with similar kinetics, but this was not sufficient to activate its downstream target eIF-2α, which initiates translation arrest, or to induce other targets like CHOP or GADD34. Both of these events preceded increased Ig synthesis, arguing this is not the signal for activating these two transducers. Targets of activating transcription factor 6 (ATF6) were up-regulated considerably later, arguing that the ATF6 branch is activated by a distinct signal. Pretreatment with LPS inhibited activation of the PERK branch by pharmacological inducers of the UPR, suggesting that differentiation-induced signals specifically silence this branch. This unique ability to differentially regulate various branches of the UPR allows B cells to accomplish distinct outcomes via the same UPR machinery

Ammattiosaamisen näytöt yrityksen ja ammattiopiston yhteistyössä

Opinnäytetyön aiheena oli selvittää, miten ammattiosaamisen näytöt toimivat paikallisen osuuskaupan ja ammattiopiston yhteistyössä koskien ravintolan salipuolen tarjoilijoita. Ammattiosaamisen näytöt ovat olleet käytössä työssäoppijoiden arvioinnissa viisi vuotta. Tavoitteena oli saada tietoa näyttöjen hyödyistä työantajanäkökulmasta katsottuna sekä löytää mahdollisia kehittämiskohteita. Opinnäytetyön teoreettisessa osassa selvennettiin työssäoppimisen ja ammattiosaamisen näytön käsitteitä, mikä on niiden merkitys ammattikoulutuksessa ja toisaalta niiden merkitys työelämälle. Lisäksi selvitettiin yritysten rekrytointikäytäntöjä ja sitä, mitä on työelämän ja oppilaitosten yhteistyö. Tutkimuksen empiirisessä osassa käytettiin puolistrukturoitua teemahaastattelua. Haastateltavat olivat paikallisen osuuskaupan ravintoloiden esimiehiä, ja haastattelut tehtiin kuudelle henkilölle. Haastattelut nauhoitettiin ja litteroitiin sanasta sanaan tietokoneelle jatkoanalyysia varten. Tutkimuksen tuloksena vahvistui se, että ammattiosaamisen näytöt ovat kaikille selkeä asia ja niistä on hyötyä sekä työnantajalle että opiskelijalle. Yhteistyö osuuskaupan ja ammattiopiton kanssa toimii hyvin, eivätkä näyttötilanteet ole aiheuttaneet suurempia ongelmia. Ainoastaan työssäoppijan osaamisen arviointi koetaan hankalana nykyisellä asteikolla. Alan ammattiopistotasoista koulutusta tarvitaan edelleen Joensuun alueella, ja tutkimuksen mukaan sitä pitäisi jopa lisätä. Koulutetun työvoiman puute ei vielä ole maakunnassa suuri ongelma verrattuna pääkaupunkiseutuun, mutta uhkakuvia on jo nyt havaittavissa. Tähän tulisi yhteistyökumppaneiden kiinnittää huomiota, jotta jatkossa Joensuun alueella koulutetaan riittävästi työvoimaa alalle.The purpose of the thesis was to find out how the collaboration between a company and vocational college works concerning vocational skills demonstrations of restaurant waiters. In addition, the task was to examine if there is any benefit of skills demonstrations for the company, and how to develop co-operation. Partners for the study are a local hotel and restaurant company and a local vocational college. The information was gathered from literature, journals, the Internet and by interviewing. In the theoretical part of the study the main issue was to explain what on-the-job learning is and what vocational skills demonstrations are, and what their consequence is for vocational education and for work life. Also how companies carry out their recruitment was clarified. Data for this study were collected by interviewing six supervisors in partner restaurants. The results of the study show that vocational skills demonstrations are perceived well without any complexities. Rather the results indicate more utilities for students, for the company and for the vocational school. The final result of this thesis was that it is important to keep on vocational education in Joensuu and even to enhance it. Now the lack of trained waiters is a fact in southern Finland. A vision is that it will be a threat also in eastern Finland in the future. To ensure professional labour for hotel and restaurant business, companies support for vocational education is essential