Cancer-associated fibroblasts from human NSCLC survive ablative doses of radiation but their invasive capacity is reduced

<p>Background: Cancer-Associated Fibroblasts (CAFs) are significant components of solid malignancies and play central roles in cancer sustainability, invasion and metastasis. In this study we have investigated the invasive capacity and matrix remodelling properties of human lung CAFs after exposure to ablative doses of ionizing radiation (AIR), equivalent to single fractions delivered by stereotactic ablative radiotherapy (SART) for medically inoperable stage-I/II non-small-cell lung cancers.</p> <p>Methods: CAFs were isolated from lung tumour specimens from 16 donors. Initially, intrinsic radiosensitivity was evaluated by checking viability and extent of DNA-damage response (DDR) at different radiation doses. The migrative and invasive capacities of CAFs were thereafter determined after a sub-lethal single radiation dose of 18 Gy. To ascertain the mechanisms behind the altered invasive capacity of cells, expression of matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) were measured in the conditioned media several days post-irradiation, along with expression of cell surface integrins and dynamics of focal contacts by vinculin-staining.</p> <p>Results: Exposing CAFs to 1 × 18 Gy resulted in a potent induction of multiple nuclear DDR foci (> 9/cell) with little resolution after 120 h, induced premature cellular senescence and inhibition of the proliferative, migrative and invasive capacity. AIR promoted MMP-3 and inhibited MMP-1 appearance to some extent, but did not affect expression of other major MMPs. Furthermore, surface expression of integrins α2, β1 and α5 was consistently enhanced, and a dramatic augmentation and redistribution of focal contacts was observed.</p> <p>Conclusions: Our data indicate that ablative doses of radiation exert advantageous inhibitory effects on the proliferative, migratory and invasive capacity of lung CAFs. The reduced motility of irradiated CAFs might be a consequence of stabilized focal contacts via integrins.</p&gt

Undervisningsformer som kan forebygge matematikkvansker

Sammendrag Formålet med denne studien har vært å undersøke hva en gruppe elever og noen lærere tenker om undervisning som skaper motivasjon og arbeidsglede i matematikkfaget, og hvordan det kan være med å påvirke å stå i det som er vanskelig. Jeg har ønsket å få innsikt i undervisningsformer som kan være med å forebygge matematikkvansker. I studien har jeg belyst følgende problemstilling: Hvilke tanker har elever og lærere om undervisning som gir elever arbeidslyst og tro på at de skal få det til i matematikk? For å besvare problemstillingen har jeg tatt utgangspunkt i en kvalitativ forskningstilnærming. Jeg har innhentet data gjennom intervjuer med tre matematikklærere og fokusgruppeintervju med fem elever. Tre av elevene er elever av den ene læreren som deltok i studien. Resultatene fra datainnsamlingen blir presentert og drøftet i tre hovedkategorier med tilhørende underkategorier: 1) utvikle forståelse og ikke bare utførelse, 2) undervisning som skaper motivasjon og som gjør at elevene klarer å stå i det som er vanskelig, 3) læringsmiljø som fremmer utvikling og troen på seg selv. Resultatene viser at lærerne er nytenkende i sin pedagogiske tilnærming. De har et dynamisk tankesett som de fremmer i sin undervisning gjennom å vise tro på at alle elever gjennom innsats kan lære og utvikle seg når undervisningen bygger på eleven sin forståelse. Videre viser resultatene at lærerne har en holdning til at mangfold i faglig nivå skaper en helhetlig undervisning. Lærerne legger til rette for en matematikkundervisning som gjør at individuelle hensyn blir ivaretatt i fellesskapet gjennom samarbeid, dialog og et grunnsyn om at feiling fremmer læring. Kognitivt krevende oppgaver med lav inngangsterskel blir presentert av lærerne på en slik måte at elevene blir indre motivert. Elevene forteller at de opplever at de lærer best når de får samarbeide med hverandre. De blir motivert av å jobbe med utforskende oppgaver som krever at de må tenke. Lærerne viser sterk tro til sin undervisningsform og det framgår av resultatene at de over tid har sett en sammenheng mellom undervisningsformen og økt motivasjon og læring. I min studie kommer det fram at læreren driver en undervisningspraksis som vektlegger et balansert forhold mellom prosedyrekunnskap og konseptuell kunnskap. Dette vil gi flere elever mulighet til å øke sin proseptuelle forståelse. Det kan være grunn til å anta at dette er en undervisningsform som vil gi elevene større glede med matematikk utover i skoleløpet

Pursuit of performance excellence: a population study of Norwegian adolescent female cross-country skiers and biathletes with disordered eating

Aim: To examine the prevalence of disordered eating (DE) among the total population of Norwegian female cross-country skiers and biathletes at the junior level, and to determine whether sociodemographic characteristics predict DE among athletes. Methods: A cross-sectional population study of Norwegian female junior cross-country skiers and biathletes (n=262), with a response rate of 86%. Descriptive statistics and logistic regression analyses explored the prevalence of DE and its relation to sports, competitive age groups, competitive status and education. DE was defined as meeting at least 1 of the following criteria from 2 subscales of the Eating Disorder Inventory-2: the Drive for Thinness score ≥15 and/or the Body Dissatisfaction score ≥14. Results: 18.7% of the athletes had DE. There was no significant difference in the occurrence of DE between the sports or the competitive age groups. Athletes who had dropped out of sports had a significantly higher occurrence of DE, while athletes who attended upper secondary schools of elite sports or general studies had a significantly higher occurrence of DE based on Drive for Thinness. Conclusions: The number of female cross-country skiers and biathletes with DE is higher than that found in previous similar studies using the same screening instruments. Type of education and competitive status are significant predictors of DE, indicating that DE in addition to having adverse effects on an athlete's health, may also lead to early dropout of sport. This indicates that health and achievement are not always compatible within sports

Pursuit of performance excellence: a population study of Norwegian adolescent female cross-country skiers and biathletes with disordered eating

Aim: To examine the prevalence of disordered eating (DE) among the total population of Norwegian female cross-country skiers and biathletes at the junior level, and to determine whether sociodemographic characteristics predict DE among athletes. Methods: A cross-sectional population study of Norwegian female junior cross-country skiers and biathletes (n=262), with a response rate of 86%. Descriptive statistics and logistic regression analyses explored the prevalence of DE and its relation to sports, competitive age groups, competitive status and education. DE was defined as meeting at least 1 of the following criteria from 2 subscales of the Eating Disorder Inventory-2: the Drive for Thinness score ≥15 and/or the Body Dissatisfaction score ≥14. Results: 18.7% of the athletes had DE. There was no significant difference in the occurrence of DE between the sports or the competitive age groups. Athletes who had dropped out of sports had a significantly higher occurrence of DE, while athletes who attended upper secondary schools of elite sports or general studies had a significantly higher occurrence of DE based on Drive for Thinness. Conclusions: The number of female cross-country skiers and biathletes with DE is higher than that found in previous similar studies using the same screening instruments. Type of education and competitive status are significant predictors of DE, indicating that DE in addition to having adverse effects on an athlete's health, may also lead to early dropout of sport. This indicates that health and achievement are not always compatible within sports

Høyhastighetsbredbånd til alle i Hedmark

Internett er en viktig ressurs i det norske samfunnet. Å bygge ut bredbåndstilbudet er en krevende prosess der flere aktører må samarbeide for å gjøre det så kostnadseffektivt som mulig. Norsk kommunikasjonsmyndighet(Nkom) ønsker at alle skal ha tilgang på høyhastighetsbredbånd og stiller opp med midler for utbyggingen. Kommunene kan få innvilget støtte fra Nkom dersom de kan dokumentere at de har et prosjektområde med behov for forbedring. Formålet med oppgaven er å lage et system som kan hjelpe Hedmark fylkeskommune og kommunene i Hedmark å kartlegge gode prosjektområder slik at de enklere kan få støtte fra Nkom for å bygge ut bredbåndstilbudet. Systemet skal samle inn informasjon om det nåværende bredbåndstilbudet og gi en oversikt over dagens situasjon slik at det blir enkelt å finne nye områder å bygge ut i

The interaction between Staphylococcus aureus SdrD and desmoglein 1 is important for adhesion to host cells

Staphylococcus aureus is known as a frequent colonizer of the skin and mucosa. Among bacterial factors involved in colonization are adhesins such as the microbial surface components recognizing adhesive matrix molecules (MSCRAMMs). Serine aspartate repeat containing protein D (SdrD) is involved in adhesion to human squamous cells isolated from the nose. Here, we identify Desmoglein 1 (Dsg1) as a novel interaction partner for SdrD. Genetic deletion of sdrD in S. aureusNCTC8325-4 through allelic replacement resulted in decreased bacterial adherence to Dsg1- expressing HaCaT cells in vitro. Complementary gain-of-function was demonstrated by heterologous expression of SdrD in Lactococcus lactis, which increased adherence to HaCaT cells. Also ectopic expression of Dsg1 in HEK293 cells resulted in increased adherence of S. aureus NCTC8325-4 in vitro. Increased adherence of NCTC8325-4, compared to NCTC8325-4ΔsdrD, to the recombinant immobilized Dsg1 demonstrated direct interaction between SdrD and Dsg1. Specificity of SdrD interaction with Dsg1 was further verified using flow cytometry and confirmed binding of recombinant SdrD to HaCaT cells expressing Dsg1 on their surface. These data demonstrate that Dsg1 is a host ligand for SdrD

Patient and public involvement in health research in Norway: a survey among researchers and patient organisations

Abstract Background Patient and public involvement (PPI) in health research may improve both the relevance and quality of the research. There is however a lack of research investigating the experiences, attitudes and barriers towards PPI in clinical research in Norway. The Norwegian Clinical Research Infrastructure Network therefore conducted a survey among researchers and PPI contributors aiming to investigate experiences with PPI and identify current challenges for successful involvement. Methods Two survey questionnaires were developed and distributed in October and November 2021. The survey targeting 1185 researchers was distributed from the research administrative system in the Regional Health Trusts. The survey targeting PPI contributors was distributed through Norwegian patient organisations, regional and national competence centers. Results The response rate was 30% among researchers and was unobtainable from PPI contributors due to the survey distribution strategy. PPI was most frequently used in the planning and conduct of the studies, and less utilized in dissemination and implementation of results. Both researchers and user representatives were generally positive to PPI, and agreed that PPI might be more useful in clinical research than in underpinning research. Researchers and PPI contributors who reported that roles and expectations were clarified in advance, were more likely to experience a common understanding of roles and responsibilities in the research project. Both groups pointed to the importance of earmarked funding for PPI activities. There was a demand for a closer collaboration between researchers and patient organisations to develop accessible tools and effective models for PPI in health research. Conclusions Surveys among clinical researchers and PPI contributors indicate overall positive attitudes towards PPI in clinical research. However, more resources, such as budget, time, and accessible tools, are needed. Clarifying roles and expectations, and creating new PPI models under resource constraints can enhance its effectiveness. PPI is underutilized in disseminating and implementing research results, presenting an opportunity for improving healthcare outcomes

Heterogeneity in γ-glutamyltransferase mRNA expression and glycan structures. Search for tumor-specific variants in human liver metastases and colon carcinoma cells

International audienceThe enzyme gamma-glutamyltransferase (GGT) is frequently overexpressed in cancer cells and tissues and has significant utility as a cancer marker. Significant heterogeneity of the enzyme has been described due to both transcriptional and post-translational variations. For possible use in diagnosis and follow-up of patients with colorectal cancer, a search was performed for specific mRNA subtypes and glycan structures of the enzyme in liver metastases. We found no differences in the distribution of three GGT mRNA subtypes (fetal liver, HepG2, placenta) in metastatic tissue and normal liver tissue. Furthermore, the three subtypes were present in leukocytes isolated from both normal individuals and cancer patients. Two colon carcinoma cell lines (Colo 205 and HCC 2998) also displayed the three forms and no consistent changes in mRNA composition were noted after butyrate-induced differentiation of the cells. Thus, neither of the GGT mRNA subforms appear to be tumor-specific, although some qualitative and quantitative variations were noted. Two distinct glycosylation features were detected for GGT in metastatic tissue in contrast to normal liver GGT; an extreme sialic acid heterogeneity and a significant increase in beta1,6GlcNAc branching. The GGT glycans from the two colon carcinoma cell lines also possessed these features. As butyrate treatment of the cells resulted in an increased sialic acid content and a reduced beta1,6GlcNAc branching, the described carbohydrate structures appear to be part of a tumor-related pattern. We were, however, unable to identify such GGT isoforms in serum from patients with advanced colorectal cancer. This indicates that their usefulness in diagnostic use is doubtful