Interferon regulatory factors 1 and 4 in T cell mediated immune modulation

The transcription factor interferon regulatory factor (IRF) 1 is essential for T helper cell 1 differentiation. Hereby, the respective Irf1 knockout mouse displays a severe immune defect and has an Th2 directed immune status per se. This effect is measurable by increased production of interleukin-4, a Th2 associated cytokine, and increased levels of immunoglobulin E. By this, the mouse is incapable to cope with intracellular pathogens and eventually dies from infection (e.g. Leishmania major infection). Allergies are also mediated by a Th2 driven immune response, therefore the question raised, whether this knockout mouse would react stronger in case of an induced allergy. To address this topic, the murine OVA model for acute asthma was used. Interestingly and despite wide-ranging analyses, it could be shown in this thesis work that the IRF1 deficiency did not result in a more severe asthma pathology. The herein presented data urgently suggest to reconsider the long-standing paradigm of asthma as only being a Th2-diven disease. Newly dicovered Th cell subsets support this opinion. The Irf1 knockout mouse not only has a defect in Th cell differentiation, but also clearly shows the requirement of IRF1 in CD8 development. The numbers of CD8+ cells in the periphery is extremely reduced, mainly due to a thymic misregulation of MHC class I. In order to reveal cell-specific functions of IRF1, a conditionally targeted mouse for Irf1 was successfully generated in the framework of this thesis. This mouse will help to address a variety of questions regarding IRF1 function in a given setting. Beside IRF1, another factor of the IRF family, namely IRF4 is important for Th differentiation. IRF4 has functions in Th2, Th9 and Th17 cell development, and the IRF4 deficient mouse is completely resistant to murine experimental autoimmune encephalomyelitis, a model for the human disease multiple sclerosis, due to the total incapacity to generate Th17 cells producing IL-17. Surprising data are shown in this thesis, in which γδ T cells from Irf4 knockout mice are nevertheless totally capable of producing IL-17. The underlying mechanism was closer investigated, and although it was not possible to reveal the actual pathway (which is apparently different from the one triggering IL-17 production in Th17 cells), the possibilities were narrowed down by excluding many other apparently obvious pathways

Short communication: Study on heavy metals (Chromium, Cadmium, Cobalt and Lead) concentration in three pelagic species of kilka (Genus Clupeonella) in the southern Caspian Sea

Environmental pollution by heavy metals has been a matter of growing concern over the last decades. Heavy metals are toxic and tend to accumulate in living organisms. In many studies, fish has been used as a sampling item to monitor the quality of ecosystems because of two reasons: 1- Fish bio-concentrate and integrate contaminant load both in time and space leading to more representative results compared to water samples, and 2- Fish represent the bio-available fraction of environmental contaminants, unlike water and sediment samples. On the other hand, humans consume fish species which makes attention to these fauna even more important. Levels of some metals in the water running in Volga River, towards the Caspian Sea, and elevated concentrations of some trace elements have been reported in sediment. Also, various pollutants have accumulated in the Caspian Sea due to effluents from coastal catchments and leakage from offshore oil production and land-based sources. ... The objective of the present study was to investigate the concentrations of chromium (Cr), cadmium (Cd), cobalt (Co) and lead (Pb) in fish muscle in the most commercially important fish species of kilka (common kilka, C. cultriventris, anchovy C. engrauliformis and bigeye kilka C. grimmi) in the Caspian Sea

Site selection for coldwater fish culture using GIS in Golestan province of Iran

In an attempt to provide a scientific basis and to discern data gaps for sustainable aquaculture expansion, we conducted a land evaluation and land use planning study to delineate areas suitable for coldwater fish culture complexes in the Golestan Province of Iran. The study was based on systematic land evaluation, a modified version of the McHarg cartographic method drawing upon ecological, social and economic factors. The minimum mapped area was 1.25t1.25Km and the Province was classified into suitable, medium, poor and unsuitable units. Elevation, slope, aspect, hydrography, temperature, evaporation, lithology, pedology, landuse, proximity to roads, protected areas and water resources were the factors included in the study. We successfully applied the method to the Province that resulted in distinguishing areas suitable for coldwater fish culture. Of the factors included in the study, proximity to roads was found to play important role in allocating an area to the activity. Also, slope, elevation, water temperature and evaporation were the other factors that helped in discerning the areas. We found that some parts of the province are amenable to the expansion of the aquaculture activities. Of the surface area of the Province, around 53 kilometers were found to be suitable for the culture. Also, 54 kilometers were moderately suitable and 68 kilometers were poorly suitable for the activity

Linking SLEUTH Urban Growth Modeling to Multi Criteria Evaluation for a Dynamic Allocation of Sites to Landfill

Abstract. Taking timely measures for management of the natural resources requires knowledge of the dynamic environment and land use practices in the rapidly changing post-industrial world. We used the SLUETH urban growth modeling and a multi-criteria evaluation (MCE) technique to predict and allocate land available to landfill as affected by the dynamics of the urban growth. The city is Gorgan, the capital of the Golestan Province of Iran. Landsat TM and ETM+ data were used to derive past changes that had occurred in the city extent. Then we employed slope, exclusion zones, urban areas, transportation network and hillshade layer of the study area in the SLEUTH modeling method to predict town sprawl up to the year 2050. We applied weighted linear combination technique of the MCE to define areas suitable for landfill. Linking the results from the two modeling methods yielded necessary information on the available land and the corresponding location for landfill given two different scenarios of town expansion up to the year 2050. These included two scenarios for city expansion and three scenarios for waste disposal. The study proved the applicability of the modeling methods and the feasibility of linking their results. Also, we showed the usefulness of the approach to decision makers in proactively taking measures in managing the likely environment change and possibly directing it towards more sustainable outcomes. This also provided a basis for dynamic land use allocation with regards to the past, present and likely future changes

Effect of plant cover on presence of Black Francolin (Francolinus francolinus) in Khouzestan Province, Southwestern Iran

Three of 6 subspecies of black francolins (Francolinus francolinus), are found throughout Iran. Habitat destruction and indiscriminate hunting as well as agricultural pesticides are among the most crucial factors threatening the populations of these birds in Khouzestan Province, southwestern Iran. Using plot sampling, this study aims to investigate different vegetative factors including plant species, percentage of species presence and dominant plant cover height on francolin presence. Sampling was carried out throughout 5 presence areas of black francolin and 2 areas lacking francolins (control areas). Results showed that frequency of Camels thorn (Alhagi cameloram), Cashew (Prosopis farcta) and African Salsola (Suaeda fruticosa) were higher in presence areas compared with other plant species. Using One Way ANOVA, it was determined that there was no significant difference between plant cover percent (P = 0.279) and dominant plant cover height (P = 0.316). However, difference of these two mentioned factors were significant in 4 seasons (P = 000 for cover height and P = 0.001 for cover percent). In fact, the highest black francolin presence was recorded at 15 – 67 and 4 – 48 for cover percent and cover height classes respectively

A dual AAV system enables the Cas9-mediated correction of a metabolic liver disease in newborn mice

Many genetic liver diseases present in newborns with repeated, often lethal, metabolic crises. Gene therapy using non-integrating viruses such as AAV is not optimal in this setting because the non-integrating genome is lost as developing hepatocytes proliferate1,2. We reasoned that newborn liver may be an ideal setting for AAV-mediated gene correction using CRISPR/Cas9. Here we intravenously infuse two AAVs, one expressing Cas9 and the other expressing a guide RNA and the donor DNA, into newborn mice with a partial deficiency in the urea cycle disorder enzyme, ornithine transcarbamylase (OTC). This resulted in reversion of the mutation in 10% (6.7% – 20.1%) of hepatocytes and increased survival in mice challenged with a high-protein diet, which exacerbates disease. Gene correction in adult OTC-deficient mice was lower and accompanied by larger deletions that ablated residual expression from the endogenous OTC gene, leading to diminished protein tolerance and lethal hyperammonemia on a chow diet