Molands- og Langangsvassdraget i Aust-Agder - næringsstofftilførsler, vannkvalitet, plankton og fiskebestander

Molands- og Langangsvassdraget er undersøkt i 1994-1996 mht. vannkvalitet, plankton, fiskebestander og næringssalttilførsler. I følge SFTs klassifiseringssystem må vannkvaliteten på de ulike stasjonene i vassdragene karakteriseres som "mindre god " til "dårlig" mht virkninger av næringssalter, "mindre god " til "nokså dårlig "mht. tarmbakterier, og "god " til "nokså dårlig" mht surhet. Sedimentene i Molandsvatn så ut til å ha meget høye konsentrasjoner av disykliske aromatiske hydrokarboner som er indikator på oljeforurensning. Det er beregnet en fosfortilførsel til Molandsvatn og Langangsvatn på hhv 730 og 1040 kg P/år. Av dette er bidraget fra landbruk og bebyggelse anslått til omkring 65%. De totale nitrogentilførslene er beregnet til 23,1 tonn for Molandsvatn og 32,7 tonn for Langangsvatn. Nitrogenbidraget fra lokale kilder er anslått til 40 %. Under elektrofiske i tilløpsbekker til Molandsvatn under tørrværsperioden i august 1995 ble det registrert fisk i Tveitebekken, Skjulestadbekken, Brekkeelva, Moenbekken og Våjebekken. Ved prøvefiske av Molandsvatn i september 1995 ble det fanget 6 aure, 821 tryte(abbor) og 49 suter. Det ble dermed fanget færre aure, men flere tryter (abbor) og suter enn ved prøvefisket i 1985/86.Arendal kommun

Territory location and quality, together with climate, affect the timing of breeding in the whitethroated dipper

Recent climate change has led to advanced spring phenology in many temperate regions. The phenological response to variation in the local environment, such as the habitat characteristics of the territories birds occupy, is less clear. The aim of this study is to understand how ecological conditions affect breeding time, and its consequences for reproduction, in a white-throated dipper Cinclus cinclus population in a river system in Norway during 34 years (1978–2011). Hatching date advanced almost nine days, indicating a response to higher temperatures and the advanced phenology in the area. Earlier breeding was found in warm springs and at lower altitudes. High population density facilitated earlier breeding close to the coast. Furthermore, when population density was low, breeding was early at territories that were rarely occupied, while in years with high density, breeding was early at territories that were frequently occupied. Also, when population density was low, earlier breeding occurred at territories that on average produced more offspring than other territories, while there was no difference in breeding time in high population years. Selection for early breeding was dependent on spring temperatures and high spring temperatures contributed to higher breeding success during the study period. We found that breeding phenology may have strong effects on fitness in the white-throated dipper, and thus that breeding time is an important ecological factor in a species that feeds mainly on aquatic rather than terrestrial prey.publishedVersio

Francisella tularensis Elicits IL-10 via a PGE2-Inducible Factor, to Drive Macrophage MARCH1 Expression and Class II Down-Regulation

Francisella tularensis is a bacterial pathogen that uses host-derived PGE2 to subvert the host's adaptive immune responses in multiple ways. Francisella-induced PGE2 acts directly on CD4 T cells to blunt production of IFN-γ. Francisella-induced PGE2 can also elicit production of a >10 kDa soluble host factor termed FTMØSN (F. tularensis macrophage supernatant), which acts on IFN-γ pre-activated MØ to down-regulate MHC class II expression via a ubiquitin-dependent mechanism, blocking antigen presentation to CD4 T cells. Here, we report that FTMØSN-induced down-regulation of MØ class II is the result of the induction of MARCH1, and that MØ expressing MARCH1 “resistant” class II molecules are resistant to FTMØSN-induced class II down-regulation. Since PGE2 can induce IL-10 production and IL-10 is the only reported cytokine able to induce MARCH1 expression in monocytes and dendritic cells, these findings suggested that IL-10 is the active factor in FTMØSN. However, use of IL-10 knockout MØ established that IL-10 is not the active factor in FTMØSN, but rather that Francisella-elicited PGE2 drives production of a >10 kDa host factor distinct from IL-10. This factor then drives MØ IL-10 production to induce MARCH1 expression and the resultant class II down-regulation. Since many human pathogens such as Salmonella typhi, Mycobacterium tuberculosis and Legionella pneumophila also induce production of host PGE2, these results suggest that a yet-to-be-identified PGE2-inducible host factor capable of inducing IL-10 is central to the immune evasion mechanisms of multiple important human pathogens

Parasite fate and involvement of infected cells in the induction of CD4+ and CD8+ T cell responses to Toxoplasma gondii

During infection with the intracellular parasite Toxoplasma gondii, the presentation of parasite-derived antigens to CD4+ and CD8+ T cells is essential for long-term resistance to this pathogen. Fundamental questions remain regarding the roles of phagocytosis and active invasion in the events that lead to the processing and presentation of parasite antigens. To understand the most proximal events in this process, an attenuated non-replicating strain of T. gondii (the cpsII strain) was combined with a cytometry-based approach to distinguish active invasion from phagocytic uptake. In vivo studies revealed that T. gondii disproportionately infected dendritic cells and macrophages, and that infected dendritic cells and macrophages displayed an activated phenotype characterized by enhanced levels of CD86 compared to cells that had phagocytosed the parasite, thus suggesting a role for these cells in priming naïve T cells. Indeed, dendritic cells were required for optimal CD4+ and CD8+ T cell responses, and the phagocytosis of heat-killed or invasion-blocked parasites was not sufficient to induce T cell responses. Rather, the selective transfer of cpsII-infected dendritic cells or macrophages (but not those that had phagocytosed the parasite) to naïve mice potently induced CD4+ and CD8+ T cell responses, and conferred protection against challenge with virulent T. gondii. Collectively, these results point toward a critical role for actively infected host cells in initiating T. gondii-specific CD4+ and CD8+ T cell responses

Betydningen av fluor for Glamslandsvassdraget, Aust-Agder

Fluorkonsentrasjonen i Glamslandsvassdraget er betydelig forhøyet (>100 ganger) i forhold til naturlige bakgrunnsnivåer i Norge. Fluorkonsentrasjonene i vassdraget er i henhold til publisert litteratur svært giftig. Sommeren/høsten 2000 ble det utført en undersøkelse i Glamslandsvassdraget. Forekomst av fisk og bunndyr synes ikke endret sammenliknet med opprinnelig naturtilstand slik denne ble dokumentert i 1968, dvs før fluorutslippet startet. Vi har således ikke kunnet påvise biologiske effekter av fluorutslippet. Årsaken til hvorfor fluor i Glamslandsvann er lite giftig bør fastslås. Det antas at fluor som tilføres vassdraget er kompleksbundet og derved lite/ikke biotilgjengelig. Dette bør undersøkes slik at avgiftingsmekanismer kan inkluderes i evalueringsgrunnlaget mhp biologisk effekt av fluor

Store Finntjenn i Aust-Agder. Vannkjemisk og biologisk utvikling i løpet av 15 år med kalking

Store Finntjenn er undersøkt kjemisk og biologisk siden 1980 og kalket regelmessig siden høsten 1981. Målet med kalkingen har vært å sikre tilstrekkelig god vannkvalitet for abborbestanden i innsjøen. Rapporten inneholder en sammenstilling av de kjemiske og biologiske dataene fra perioden 1980-1996, for å dokumentere eventuelle langtidseffekter av kalking både på vannkjemi og på innsjøens økosystem. I de første årene etter kalkingen kunne det registreres et midlertidig oppsving i biomassen av både planteplankton og bunndyr, sannsynligvis pga. økt mikrobiell omsetning av akkumulert organisk materiale. De biotiske samfunnene i innsjøen har beveget seg i retning av et naturlig, uforsuret samfunn, men uten helt å oppnå den stabilitet og artssammensetning som kjennetegner disse systemene. Relativt store svingninger i forekomst/tetthet av ulike organismegrupper, antyder at innsjø-økosystemet fremdeles ikke er intakt, men fortsatt preget av tidvis ikke-optimal vannkvalitet. Stabilisering av vannkvaliteten gjennom året er viktig for å kunne oppnå økologisk balanse i et kalket innsjøsystem. I Store Finntjenn anbefales det derfor at en fortsetter med kalking hvert år, slik som det er praktisert siden 1995

Integrated functional and spatial profiling of tumour immune responses induced by immunotherapy: the iPROFILER platform.

Background Cancer immunotherapy elicits functional activation and changes in immune cell distribution in cancer. Tumour heterogeneity is a reason for treatment failure but is difficult to capture in experimental settings. This proof-of-principle study describes the integrated functional and digital spatial profiling platform iPROFILER to capture in-situ immune activation patterns with high precision. Materials and methods iPROFILER combines an algorithm-based image analysis approach for spatial profiling with functional analyses of patient-derived tumour fragments (PDTFs). This study utilized a folate receptor 1 (FOLR1)xCD3 bispecific antibody in dual-affinity re-targeting (DART) format as a tool for inducing T-cell responses in patient tumour samples, and an in-depth investigation of the immune perturbations induced in the tumour microenvironment was performed. Results Ex-vivo DART stimulation induces upregulation of multiple activation markers in CD4+ and CD8+ T-cell populations and secretion of pro-inflammatory cytokines in FOLR1-positive tumour specimens. This response was reduced or absent in tissue samples that did not express FOLR1. Immunological responses were driven by a strong induction of interferon gamma (IFNγ) and IFNγ-induced chemokines suggestive of activation of cytotoxic or Th1-like T cells. Ex-vivo DART treatment led to a numerical increase in effector T cells and an upregulation of immune activation markers in the tumour microenvironment as captured by digital image analysis. Analysis of immune activation in tumour and stromal regions further supported the potential of the platform to measure local differences in cell-type-specific activation patterns. Conclusions iPROFILER effectively combines functional and spatial readouts to investigate immune responses ex vivo in human tumour samples

Targeting B-cell neoplasia with T-cell receptors recognizing a CD20-derived peptide on patient-specific HLA

T cells engineered to express chimeric antigen receptors (CARs) targeted to CD19 are effective in treatment of B-lymphoid malignancies. However, CARs recognize all CD19 positive (pos) cells, and durable responses are linked to profound depletion of normal B cells. Here, we designed a strategy to specifically target patient B cells by utilizing the fact that T-cell receptors (TCRs), in contrast to CARs, are restricted by HLA. Two TCRs recognizing a peptide from CD20 (SLFLGILSV) in the context of foreign HLA-A*02:01 (CD20p/HLA-A2) were expressed as 2A-bicistronic constructs. T cells re-directed with the A23 and A94 TCR constructs efficiently recognized malignant HLA-A2pos B cells endogenously expressing CD20, including patient-derived follicular lymphoma and chronic lymphocytic leukemia (CLL) cells. In contrast, a wide range of HLA-A2(pos)CD20neg cells representing different tissue origins, and HLA-A2(neg)CD20pos cells, were not recognized. Cytotoxic T cells re-directed with CD20p/HLA-A2-specific TCRs or CD19 CARs responded with similar potencies to cells endogenously expressing comparable levels of CD20 and CD19. The CD20p/HLA-A2-specific TCRs recognized CD20p bound to HLA-A2 with high functional avidity. The results show that T cells expressing CD20p/HLA-A2-specific TCRs efficiently and specifically target B cells. When used in context of an HLA-haploidentical allogeneic stem cell transplantation where the donor is HLA-A2(neg) and the patient HLA-A2(pos), these T cells would selectively kill patient-derived B cells and allow reconstitution of the B-cell compartment with HLA-A2(neg) donor cells. These results should pave the way for clinical testing of T cells genetically engineered to target malignant B cells without permanent depletion of normal B cells

Overvåking av langtransporterte forurensninger 2007. Sammendragsrapport

Rapporten presenterer sammendrag av resultatene for 2007 fra tre overvåkingsprogrammer: “Overvåking av langtrans¬portert forurenset luft og nedbør”, ”Overvåkingsprogram for skogskader” (OPS) og “Program for terrestrisk naturovervåking” (TOV)