Bacteria Penetrate the Inner Mucus Layer before Inflammation in the Dextran Sulfate Colitis Model

Protection of the large intestine with its enormous amount of commensal bacteria is a challenge that became easier to understand when we recently could describe that colon has an inner attached mucus layer devoid of bacteria (Johansson et al. (2008) Proc. Natl. Acad. Sci. USA 105, 15064-15069). The bacteria are thus kept at a distance from the epithelial cells and lack of this layer, as in Muc2-null mice, allow bacteria to contact the epithelium. This causes colitis and later on colon cancer, similar to the human disease Ulcerative Colitis, a disease that still lacks a pathogenetic explanation. Dextran Sulfate (DSS) in the drinking water is the most widely used animal model for experimental colitis. In this model, the inflammation is observed after 3-5 days, but early events explaining why DSS causes this has not been described.When mucus formed on top of colon explant cultures were exposed to 3% DSS, the thickness of the inner mucus layer decreased and became permeable to 2 microm fluorescent beads after 15 min. Both DSS and Dextran readily penetrated the mucus, but Dextran had no effect on thickness or permeability. When DSS was given in the drinking water to mice and the colon was stained for bacteria and the Muc2 mucin, bacteria were shown to penetrate the inner mucus layer and reach the epithelial cells already within 12 hours, long before any infiltration of inflammatory cells.DSS thus causes quick alterations in the inner colon mucus layer that makes it permeable to bacteria. The bacteria that reach the epithelial cells probably trigger an inflammatory reaction. These observations suggest that altered properties or lack of the inner colon mucus layer may be an initial event in the development of colitis

Diet in 1-year-old farm and control children

BACKGROUND: A farming environment confers strong protection against allergy development. We have previously shown that farming mothers consume more full-fat dairy than control mothers, who instead consume more low-fat dairy, margarine, and oils; margarine and oil intake was associated with increased risk of allergy development in their children. OBJECTIVES: The aims of this study were to investigate the differences in diet between children in farming and control families at 1 year of age, to investigate the relation between the diets of the mothers and their children, and to relate the children's diet to allergy development. DESIGN: The diet of 1-year-old children from dairy farming families (n=28) and from control families in the same rural area (n=37) was assessed by 24-h dietary recalls, followed by 24-h food diaries. Allergy was diagnosed by pediatricians at 3 years of age using strict predefined criteria. RESULTS: Farm children had a higher intake of farm milk, whole cream, cholesterol, saturated fat, and fat in total and tended to eat more butter, while controls consumed more carbohydrates and poultry and tended to eat more margarine. Farm children also had higher intakes of homemade porridge/gruel, oily fish, and iodine. The intake of butter and whole milk in children and mothers correlated significantly in farm families but not in controls. A weak negative association was found between seafood intake and allergy development, while allergy was positively associated with the intake of pork as well as zinc in the control group; these intakes also correlated with each other. CONCLUSIONS: Consistent with mothers in farming families, the children consumed more full-fat dairy and saturated fat than did controls, but this could not be linked to the low risk of allergy in the farming group. Seafood intake might protect against allergy development, in accordance with earlier findings

11q deletion or ALK activity curbs DLG2 expression to maintain an undifferentiated state in neuroblastoma

High-risk neuroblastomas typically display an undifferentiated or poorly differentiated morphology. It is therefore vital to understand molecular mechanisms that block the differentiation process. We identify an important role for oncogenic ALK-ERK1/2-SP1 signaling in the maintenance of undifferentiated neural crest-derived progenitors through the repression of DLG2, a candidate tumor suppressor gene in neuroblastoma. DLG2 is expressed in the murine "bridge signature'' that represents the transcriptional transition state when neural crest cells or Schwann cell precursors differentiate to chromaffin cells of the adrenal gland. We show that the restoration of DLG2 expression spontaneously drives neuroblastoma cell differentiation, high-lighting the importance of DLG2 in this process. These findings are supported by genetic analyses of high-risk 11q deletion neuroblastomas, which identified genetic lesions in the DLG2 gene. Our data also suggest that further exploration of other bridge genes may help elucidate the mechanisms underlying the differentiation of NC-derived progenitors and their contribution to neuroblastomas

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

”men Gud i himmelen, vad förstår han av detta?” - En kvalitativ studie, utifrån ett barnperspektiv, om tolkanvändandet vid Socialjouren i Göteborg.

Syftet med studien var att undersöka hur sex socialsekreterare vid socialjouren i Göteborg använder sig av tolk vid akuta omhändertaganden och placeringar av barn med annat modersmål än svenska. Vi har använt oss av kvalitativ ansats för att undersöka detta eftersom vi ansåg denna metod bäst bemöta vårt syfte och frågeställning och ge oss en möjlighet att ställa följdfrågor och få djupgående svar av våra informanter. Vi har använt artiklarna tre och tolv i Barnkonventionen som tema och sedan analyserat vår empiri utifrån kommunikationsteori, barnets åldrar, kristeori och teori om dagordningsmakt då vi ansåg att dessa ingångsspår tillsammans ringar in de flesta av de faktorer man som socialsekreterare arbetar utifrån med barn. Resultat och analys av empirin visade att socialsekreterarna har som mål att jobba utifrån barnens bästa och att tankesättet om vad som är barnets bästa är implementerat i deras arbete. Detta framgick tydligt hos samtliga av våra informanter liksom ansatsen att alla barn ska ges information och tillhandahållas möjligheter att uttrycka sin åsikt i enlighet med barnkonventionen. Paradoxalt nog visade resultatet och analysen även att det inte alltid är så enkelt att överföra detta i praktiken. Detta då bedömningen om tolk görs av enskild handläggare från fall till fall. Det finns inte heller några riktlinjer på Socialjouren för när och hur man skall använda tolk eller inte. Detta innebar för det enskilda barnet att hens möjligheter att få information delgiven på sitt språk liksom rätten att få uttrycka sin åsikt var avhängigt den enskilda socialarbetarens bedömning om behov av tolk fanns. I praktiken innebar detta att det blev en distinktion mellan barn med svenska som modersmål och barn med annat modersmål än svenska då svenska barn inte behöver tolk för att förstå. Vår studie visade också att åldern spelade en relativt stor roll för vem som ansågs ha behov av tolk. I samtal med små barn användes inte tolk i större utsträckning. Till barn med svenska som modersmål diskuterades åldern utifrån på vilket sätt man skulle uttrycka informationen till det yngre barnet, inte huruvida åldern hade betydelse för att ens ge information. Återigen visades en skillnad på hur man arbetade med barn baserat på deras modersmål. Denna åtskillnad anser vi omedveten men ändock viktig att lyfta

det var som att titta på en bilolycka på håll, man visste vad som skulle hända

Syfte: Vårt syfte med uppsatsen var att vi ville ta reda på de bakomliggande faktorerna till varför just lärare blir sjukskrivna på grund av utbrändhet i så stor utsträckning. Vi ville ta reda på vad lärare som själva blivit utbrända trodde var de bakomliggande orsakerna till att just de blev sjukskrivna samt jämföra med vad litteraturen säger om denna problematik. Huvudfråga: Vilka faktorer är det som uppges vara de främsta orsakerna till att lärare blir sjukskrivna på grund av utbrändhet? Metod och material: Djupintervjuer fördelade på kön, år inom läraryrket, typ av tjänst och ålder. Material som vi har använt oss av är; böcker, rapporter och forskning skrivna inom området utbrändhet eller utmattningsdepression. Resultat: Vi kan klart och tydligt se ett samband mellan personlighet och utbrändhet. Tvärtemot vad litteraturen säger verkar det vara framför allt högpresterande och väldigt ambitiösa människor som blir utbrända. Inte heller verkar relationer till elever och föräldrar vara en bakomliggande faktor till utbrändhet. Däremot kan styrmedel ovanifrån och ledningsproblem ha en negativ inverkan. Betydelse för läraryrket: Då vi genom våra intervjuer kan se att en bättre introduktion av nyutexaminerade lärare hade kunnat förminska risken för sjukskrivning på grund av utbrändhet radikalt är undersökningen i allra högsta grad relevant för läraryrket. Med introduktion menar vi stöd och handledning från överordnad och kollegor samt tidigare inhämtad kunskap från Lärarutbildningen. Vi har också kunna lära oss mycket av dem som vi har intervjuat. Bland annat att det är viktigt att be om hjälp tills man får det

Animal personality in ants : Does the red wood ant (Formica rufa) express personality traits?

A recent theory within behavioural ecology suggests that some animal behaviour traits are consistent over time and over different contexts as part of an animals’ “personality”. Animal personality has generally been accepted within vertebrates, but the idea of invertebrates expressing personality has long been meet with scepticism. In this study, I investigate if red wood ants (Formica rufa) show exploratory and bold behaviours that fulfil the personality criteria. Moreover, I test if this species prefers dark surfaces instead of white surfaces (scototaxis). My experiment included tests of 30 ants and two different behaviour trials targeting exploration and boldness that repeated over three different time periods. My results shows that the exploratory behaviours were correlated between trials conducted at different times and therefore, that this behaviour was repeatable. It was also clear that the red wood ant consistently showed large between individuals, indicating difference in personality. However, the studied ants did not show preferences for dark surfaces and the performance in the scototaxis trial did not correlate with any other measurable behaviour. The result of this study suggests that Formica rufa show behaviours that match the animal personality criteria for exploratory behaviour, but my result could not validate that bold behaviours were repeatable across time and context.

Animal personality in ants : Does the red wood ant (Formica rufa) express personality traits?

A recent theory within behavioural ecology suggests that some animal behaviour traits are consistent over time and over different contexts as part of an animals’ “personality”. Animal personality has generally been accepted within vertebrates, but the idea of invertebrates expressing personality has long been meet with scepticism. In this study, I investigate if red wood ants (Formica rufa) show exploratory and bold behaviours that fulfil the personality criteria. Moreover, I test if this species prefers dark surfaces instead of white surfaces (scototaxis). My experiment included tests of 30 ants and two different behaviour trials targeting exploration and boldness that repeated over three different time periods. My results shows that the exploratory behaviours were correlated between trials conducted at different times and therefore, that this behaviour was repeatable. It was also clear that the red wood ant consistently showed large between individuals, indicating difference in personality. However, the studied ants did not show preferences for dark surfaces and the performance in the scototaxis trial did not correlate with any other measurable behaviour. The result of this study suggests that Formica rufa show behaviours that match the animal personality criteria for exploratory behaviour, but my result could not validate that bold behaviours were repeatable across time and context.